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112-402: 1604 13137 ENSG00000196352 ENSMUSG00000026401 P08174 Q61476 NM_001300903 NM_001300904 NM_007827 NM_001317361 NP_000565 NP_001108224 NP_001287831 NP_001287832 NP_001287833 NP_001304290 NP_031853 NP_001391877 Complement decay-accelerating factor , also known as CD55 or DAF , is a protein that, in humans, is encoded by

224-516: A carboxyl group, and a variable side chain are bonded . Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids , have a great variety of chemical structures and properties; it is the combined effect of all of

336-470: A gene may be duplicated before it can mutate freely. However, this can also lead to complete loss of gene function and thus pseudo-genes . More commonly, single amino acid changes have limited consequences although some can change protein function substantially, especially in enzymes . For instance, many enzymes can change their substrate specificity by one or a few mutations. Changes in substrate specificity are facilitated by substrate promiscuity , i.e.

448-552: A combination of sequence, structure and function, and they can be combined in many different ways. In an early study of 170,000 proteins, about two-thirds were assigned at least one domain, with larger proteins containing more domains (e.g. proteins larger than 600 amino acids having an average of more than 5 domains). Most proteins consist of linear polymers built from series of up to 20 different L -α- amino acids. All proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group,

560-556: A dark brown, nearly black coat. They are more sensitive to noise and odours and are more likely to bite than the more docile laboratory strains such as BALB/c . Group-housed C57BL/6 mice (and other strains) display barbering behaviour, which used to be seen as a sign of dominance. However, it is now known that this is more of a stereotypical behaviour triggered by stress, comparable to trichotillomania in humans or feather plucking in parrots. Mice that have been barbered extensively can have large bald patches on their bodies, commonly around

672-403: A defined conformation . Proteins can interact with many types of molecules, including with other proteins , with lipids , with carbohydrates , and with DNA . It has been estimated that average-sized bacteria contain about 2 million proteins per cell (e.g. E. coli and Staphylococcus aureus ). Smaller bacteria, such as Mycoplasma or spirochetes contain fewer molecules, on

784-834: A detailed review of the vegetable proteins at the Connecticut Agricultural Experiment Station . Then, working with Lafayette Mendel and applying Liebig's law of the minimum , which states that growth is limited by the scarcest resource, to the feeding of laboratory rats, the nutritionally essential amino acids were established. The work was continued and communicated by William Cumming Rose . The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, including those of blood, egg whites, and various toxins, as well as digestive and metabolic enzymes obtained from slaughterhouses. In

896-447: A good model for early-stage AD because they show amyloidogenesis and working memory impairments linked to age but do not show neuronal degeneration. The absence of cell death suggests that changes in typical cellular signaling cascades involved in learning and synaptic plasticity are probably linked to the memory phenotype. Associative learning impairments are exacerbated when Tg2576 mice are crossed with PS1 transgenic animals that possess

1008-478: A little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation , whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable 3D structure. But the boundary between the two is not well defined and usually lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of

1120-463: A lower neutrophil enzymatic capacity, lower activity of the complement system , and a different set of pentraxins involved in the inflammatory process ; and lack genes for important components of the immune system, such as IL-8 , IL-37 , TLR10 , ICAM-3 , etc. Laboratory mice reared in specific-pathogen-free (SPF) conditions usually have a rather immature immune system with a deficit of memory T cells . These mice may have limited diversity of

1232-405: A number of researchers. Regarding experiments on mice, some researchers have complained that "years and billions of dollars have been wasted following false leads" as a result of a preoccupation with the use of these animals in studies. Mice differ from humans in several immune properties: mice are more resistant to some toxins than humans; have a lower total neutrophil fraction in the blood ,

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1344-410: A particular cell or cell type is known as its proteome . The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by

1456-500: A protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments can provide information about the physiological role of a protein in the context of a cell or even a whole organism . In silico studies use computational methods to study proteins. Proteins may be purified from other cellular components using

1568-411: A protein is defined by the sequence of a gene, which is encoded in the genetic code . In general, the genetic code specifies 20 standard amino acids; but in certain organisms the genetic code can include selenocysteine and—in certain archaea — pyrrolysine . Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification , which alters

1680-539: A protein that fold into distinct structural units. Domains usually also have specific functions, such as enzymatic activities (e.g. kinase ) or they serve as binding modules (e.g. the SH3 domain binds to proline-rich sequences in other proteins). Short amino acid sequences within proteins often act as recognition sites for other proteins. For instance, SH3 domains typically bind to short PxxP motifs (i.e. 2 prolines [P], separated by two unspecified amino acids [x], although

1792-486: A role in biological recognition phenomena involving cells and proteins. Receptors and hormones are highly specific binding proteins. Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse . Membrane proteins contain internal channels that allow such molecules to enter and exit

1904-406: A series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a " His-tag "),

2016-535: A single breeding pair. Inbred mice have several traits that make them ideal for research purposes. They are isogenic , meaning that all animals are nearly genetically identical. Approximately 98.7% of the genetic loci in the genome are homozygous , so there are probably no "hidden" recessive traits that could cause problems. They also have very unified phenotypes due to this stability. Many inbred strains have well documented traits that make them ideal for specific types of research. The following table shows

2128-432: A solution known as a crude lysate . The resulting mixture can be purified using ultracentrifugation , which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles , and nucleic acids . Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate

2240-616: A standard for their care and use. Compliance with the PHS is required for a research project to receive federal funding. PHS policy is administered by the Office of Laboratory Animal Welfare. Many academic research institutes seek accreditation voluntarily, often through the Association for Assessment and Accreditation of Laboratory Animal Care , which maintains the standards of care found within The Guide for

2352-525: A tunnel or cupped hands is advocated. In behavioural tests, tail-handled mice show less willingness to explore and to investigate test stimuli, as opposed to tunnel-handled mice which readily explore and show robust responses to test stimuli. In nature, mice are usually herbivores , consuming a wide range of fruit or grain. However, in laboratory studies it is usually necessary to avoid biological variation and to achieve this, laboratory mice are almost always fed only commercial pelleted mouse feed. Food intake

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2464-441: A variety of techniques such as ultracentrifugation , precipitation , electrophoresis , and chromatography ; the advent of genetic engineering has made possible a number of methods to facilitate purification. To perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis , in which a cell's membrane is disrupted and its internal contents released into

2576-632: Is 20 days. A fertile postpartum estrus occurs 14–24 hours following parturition , and simultaneous lactation and gestation prolongs gestation by 3–10 days owing to delayed implantation. The average litter size is 10–12 during optimum production, but is highly strain-dependent. As a general rule, inbred mice tend to have longer gestation periods and smaller litters than outbred and hybrid mice. The young are called pups and weigh 0.5–1.5 g (0.018–0.053 oz) at birth, are hairless, and have closed eyelids and ears. Pups are weaned at 3 weeks of age when they weigh about 10–12 g (0.35–0.42 oz). If

2688-493: Is a determinant for the Cromer blood group system. DAF is a 70 kDa membrane protein that attaches to the cell membrane via a glycophosphatidylinositol (GPI) anchor. DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2, CCP3, CCP4 and three consecutive lysine residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of

2800-430: Is a group in which all members are as nearly as possible genetically identical. In laboratory mice, this is accomplished through inbreeding . By having this type of population, it is possible to conduct experiments on the roles of genes, or conduct experiments that exclude genetic variation as a factor. In contrast, outbred populations are used when identical genotypes are unnecessary or a population with genetic variation

2912-518: Is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species Mus musculus . They are the most commonly used mammalian research model and are used for research in genetics , physiology , psychology , medicine and other scientific disciplines . Mice belong to the Euarchontoglires clade, which includes humans . This close relationship,

3024-410: Is also possible. Each route has a recommended injection site, approximate needle gauge and recommended maximum injected volume at a single time at one site, as given in the table below: To facilitate intravenous injection into the tail, laboratory mice can be carefully warmed under heat lamps to vasodilate the vessels. A common regimen for general anesthesia for the house mouse is ketamine (in

3136-531: Is an albino laboratory-bred strain from which a number of common substrains are derived. With over 200 generations bred since 1920, BALB/c mice are distributed globally and are among the most widely used inbred strains used in animal experimentation . BALB/c are noted for displaying high levels of anxiety and for being relatively resistant to diet-induced atherosclerosis , making them a useful model for cardiovascular research. Male BALB/c mice are aggressive and will fight other males if housed together. However,

3248-465: Is approximately 15 g (0.53 oz) per 100 g (3.5 oz) of body weight per day; water intake is approximately 15 ml (0.53 imp fl oz; 0.51 US fl oz) per 100 g of body weight per day. Routes of administration of injections in laboratory mice are mainly subcutaneous , intraperitoneal and intravenous . Intramuscular administration is not recommended due to small muscle mass. Intracerebral administration

3360-439: Is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel , the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of different tags have been developed to help researchers purify specific proteins from complex mixtures. Laboratory mouse The laboratory mouse or lab mouse

3472-562: Is dictated by the nucleotide sequence of their genes , and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide . A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides . The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues in

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3584-628: Is found in hard or filamentous structures such as hair , nails , feathers , hooves , and some animal shells . Some globular proteins can also play structural functions, for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that make up the cytoskeleton , which allows the cell to maintain its shape and size. Other proteins that serve structural functions are motor proteins such as myosin , kinesin , and dynein , which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and

3696-469: Is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second. The process of synthesizing a protein from an mRNA template is known as translation . The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges"

3808-461: Is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure . Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction. Most proteins fold into unique 3D structures. The shape into which a protein naturally folds is known as its native conformation . Although many proteins can fold unassisted, simply through

3920-404: Is often enormous—as much as 10 -fold increase in rate over the uncatalysed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme). The molecules bound and acted upon by enzymes are called substrates . Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with

4032-608: Is required, and are usually referred to as stocks rather than strains . Over 400 standardized, inbred strains have been developed. Most laboratory mice are hybrids of different subspecies, most commonly of Mus musculus domesticus and Mus musculus musculus . Laboratory mice can have a variety of coat colours, including agouti, black and albino . Many (but not all) laboratory strains are inbred. The different strains are identified with specific letter-digit combinations; for example C57BL/6 and BALB/c . The first such inbred strains were produced in 1909 by Clarence Cook Little , who

4144-425: Is spontaneous. The duration of the estrous cycle is 4–5 days and lasts about 12 hours, occurring in the evening. Vaginal smears are useful in timed matings to determine the stage of the estrous cycle. Mating can be confirmed by the presence of a copulatory plug in the vagina up to 24 hours post-copulation. The presence of sperm on a vaginal smear is also a reliable indicator of mating. The average gestation period

4256-949: Is the Tg2576 strain of mice. The K670M and N671L double mutations seen in the human 695 splice-variant of the amyloid precursor protein (APP) are expressed by this strain. A hamster prion protein gene promoter , predominantly in neurons, drives the expression. When compared to non-transgenic littermates, Tg2576 mice show a five-fold rise in Aβ40 and a 10- to 15-fold increase in Aβ42/43. These mice develop senile plaques linked to cellular inflammatory responses because their brains have approximately five times as much transgenic mutant human APP than indigenous mouse APP. The mice exhibit main characteristics of Alzheimer's disease (AD), such as increased generation of amyloid fibrils with aging, plaque formation, and impaired hippocampus learning and memory. Tg2576 mice are

4368-532: Is the code for methionine . Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon. Genes encoded in DNA are first transcribed into pre- messenger RNA (mRNA) by proteins such as RNA polymerase . Most organisms then process the pre-mRNA (also known as a primary transcript ) using various forms of post-transcriptional modification to form

4480-493: Is unusually sensitive to pain and to cold, and analgesic medications are less effective in this strain. Unlike most laboratory mouse strains, the C57BL/6 drinks alcoholic beverages voluntarily. It is more susceptible than average to morphine addiction , atherosclerosis , and age-related hearing loss . When compared directly to BALB/c mice, C57BL/6 mice also express both a robust response to social rewards and empathy. BALB/c

4592-401: Is used as a receptor by some coxsackieviruses and other enteroviruses . Recombinant soluble DAF- Fc has been tested in mice as an anti-enterovirus therapy for heart damage; however, the human enterovirus that was tested binds much more strongly to human DAF than to mouse or rat DAF. Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind

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4704-663: The American Veterinary Medical Association issued new guidelines for CO 2 induction, stating that a flow rate of 10% to 30% volume/min is optimal for euthanasing laboratory mice. A recent study detected a murine astrovirus in laboratory mice held at more than half of the US and Japanese institutes investigated. Murine astrovirus was found in nine mice strains, including NSG , NOD-SCID , NSG-3GS , C57BL6 - Timp-3 , uPA-NOG , B6J , ICR, Bash2 , and BALB/C , with various degrees of prevalence. The pathogenicity of

4816-551: The CD55 gene . DAF regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during activation of C4 ( classical or lectin pathway) or C3 ( alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2a C3-convertase , and interaction of DAF with C3b of

4928-538: The alternate complement pathway . CCP2 and CCP3 alone are involved in its inhibition of the classical pathway . Because DAF is a GPI -anchored protein, its expression is reduced in persons with mutations that reduce GPI levels such as those with paroxysmal nocturnal hemoglobinuria (PNH). In PNH disorder, red blood cells with very low levels of DAF and CD59 undergo complement -mediated hemolysis. Symptoms include low red blood cell count (anemia), fatigue, and episodes of dark colored urine and other complications. DAF

5040-486: The amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da . Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body, because it was generally believed that "flesh makes flesh." Around 1862, Karl Heinrich Ritthausen isolated the amino acid glutamic acid . Thomas Burr Osborne compiled

5152-475: The microbiota , which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, herpesviruses ) are activated in humans, but not in SPF mice with septic complications and may change the resistance to bacterial coinfections . "Dirty" mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in

5264-644: The muscle sarcomere , with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids. Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis , which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield. Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. These methods are useful in laboratory biochemistry and cell biology , though generally not for commercial applications. Chemical synthesis

5376-645: The sperm of many multicellular organisms which reproduce sexually . They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport. A key question in molecular biology is how proteins evolve, i.e. how can mutations (or rather changes in amino acid sequence) lead to new structures and functions? Most amino acids in a protein can be changed without disrupting activity or function, as can be seen from numerous homologous proteins across species (as collected in specialized databases for protein families , e.g. PFAM ). In order to prevent dramatic consequences of mutations,

5488-537: The white-footed mouse ( Peromyscus leucopus ) and the North American deer mouse ( Peromyscus maniculatus ). Mice have been used in biomedical research since the 17th century when William Harvey used them for his studies on reproduction and blood circulation and Robert Hooke used them to investigate the biological consequences of an increase in air pressure. During the 18th century Joseph Priestley and Antoine Lavoisier both used mice to study respiration . In

5600-493: The 1700s by Antoine Fourcroy and others, who often collectively called them " albumins ", or "albuminous materials" ( Eiweisskörper , in German). Gluten , for example, was first separated from wheat in published research around 1747, and later determined to exist in many plants. In 1789, Antoine Fourcroy recognized three distinct varieties of animal proteins: albumin , fibrin , and gelatin . Vegetable (plant) proteins studied in

5712-562: The 1950s, the Armour Hot Dog Company purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists; this gesture helped ribonuclease A become a major target for biochemical study for the following decades. The understanding of proteins as polypeptides , or chains of amino acids, came through the work of Franz Hofmeister and Hermann Emil Fischer in 1902. The central role of proteins as enzymes in living organisms that catalyzed reactions

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5824-428: The 19th century Gregor Mendel carried out his early investigations of inheritance on mouse coat color but was asked by his superior to stop breeding in his cell "smelly creatures that, in addition, copulated and had sex". He then switched his investigations to peas but, as his observations were published in a somewhat obscure botanical journal, they were virtually ignored for over 35 years until they were rediscovered in

5936-498: The 20,000 or so proteins encoded by the human genome, only 6,000 are detected in lymphoblastoid cells. Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG ( adenine – uracil – guanine )

6048-646: The 20th and 21st Centuries. The Jackson Laboratory in Bar Harbor, Maine is currently one of the world's largest suppliers of laboratory mice, at around 3 million mice a year. The laboratory is also the world's source for more than 8,000 strains of genetically defined mice and is home of the Mouse Genome Informatics database. Breeding onset occurs at about 50 days of age in both females and males, although females may have their first estrus at 25–40 days. Mice are polyestrous and breed year round; ovulation

6160-499: The A246E FAD mutation. This crosses promotes the build-up of amyloid and plaque development in the CNS. This lends credence to the theory that AD pathogenesis is influenced by the interplay between APP and PS-1 gene products. Although Tg2576 mice do not perfectly replicate late-stage AD with cell death, they do offer a platform for researching the physiology and biochemistry of the illness.With

6272-451: The BALB/Lac substrain is much more docile. Most BALB/c mice substrains have a long reproductive life-span. There are noted differences between different BALB/c substrains, though these are thought to be due to mutation rather than genetic contamination. The BALB/cWt is unusual in that 3% of progeny display true hermaphroditism . A useful model for Alzheimer's disease (AD) in the lab

6384-603: The Care and Use of Laboratory Animals and the PHS policy. This accreditation is, however, not a prerequisite for federal funding, unlike the actual compliance. While mice are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. For example, the utility of rodents in testing for sepsis , burns , inflammation , stroke , ALS , Alzheimer's disease , diabetes , cancer , multiple sclerosis , Parkinson's disease , and other illnesses has been called into question by

6496-516: The EC number system provides a functional classification scheme. Similarly, the gene ontology classifies both genes and proteins by their biological and biochemical function, but also by their intracellular location. Sequence similarity is used to classify proteins both in terms of evolutionary and functional similarity. This may use either whole proteins or protein domains , especially in multi-domain proteins . Protein domains allow protein classification by

6608-707: The U.K. are published each year. In the U.K. in 2013, there were a total of 3,077,115 regulated procedures undertaken on mice in scientific procedure establishments, licensed under the Act. In the U.S., laboratory mice are not regulated under the Animal Welfare Act administered by the USDA APHIS . However, the Public Health Service Act (PHS) as administered by the National Institutes of Health does offer

6720-709: The ability of many enzymes to bind and process multiple substrates . When mutations occur, the specificity of an enzyme can increase (or decrease) and thus its enzymatic activity. Thus, bacteria (or other organisms) can adapt to different food sources, including unnatural substrates such as plastic. Methods commonly used to study protein structure and function include immunohistochemistry , site-directed mutagenesis , X-ray crystallography , nuclear magnetic resonance and mass spectrometry . The activities and structures of proteins may be examined in vitro , in vivo , and in silico . In vitro studies of purified proteins in controlled environments are useful for learning how

6832-459: The ability to accurately extrapolate findings to humans. Researchers have also noted that many studies involving mice are poorly designed, leading to questionable findings. Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done are omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include

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6944-405: The addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine . Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of

7056-595: The alpha carbons are roughly coplanar . The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone. The end with a free amino group is known as the N-terminus or amino terminus, whereas the end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus (the sequence of the protein is written from N-terminus to C-terminus, from left to right). The words protein , polypeptide, and peptide are

7168-464: The alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane attack complex . This glycoprotein is broadly distributed among hematopoietic and non-hematopoietic cells. It

7280-531: The amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity. The amino acids in a polypeptide chain are linked by peptide bonds . Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone. The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that

7392-452: The associated high homology with humans, their ease of maintenance and handling, and their high reproduction rate, make mice particularly suitable models for human-oriented research. The laboratory mouse genome has been sequenced and many mouse genes have human homologues. Lab mice are sold at pet stores for snake food and can also be kept as pets . Other mouse species sometimes used in laboratory research include two American species,

7504-574: The binding of a substrate molecule to an enzyme's active site , or the physical region of the protein that participates in chemical catalysis. In solution, proteins also undergo variation in structure through thermal vibration and the collision with other molecules. Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins , fibrous proteins , and membrane proteins . Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen ,

7616-570: The body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin , which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom . Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play

7728-558: The cell is as enzymes , which catalyse chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism , as well as manipulating DNA in processes such as DNA replication , DNA repair , and transcription . Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification. About 4,000 reactions are known to be catalysed by enzymes. The rate acceleration conferred by enzymatic catalysis

7840-436: The cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell. Antibodies are protein components of an adaptive immune system whose main function is to bind antigens , or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in

7952-752: The cell's machinery through the process of protein turnover . A protein's lifespan is measured in terms of its half-life and covers a wide range. They can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal or misfolded proteins are degraded more rapidly either due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids , proteins are essential parts of organisms and participate in virtually every process within cells . Many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism . Proteins also have structural or mechanical functions, such as actin and myosin in muscle and

8064-450: The cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions. Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins ; for example, collagen and elastin are critical components of connective tissue such as cartilage , and keratin

8176-621: The chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure: Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as " conformations ", and transitions between them are called conformational changes. Such changes are often induced by

8288-441: The chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA , most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. The set of proteins expressed in

8400-547: The closest non- primate relatives of humans along with lagomorphs , treeshrews , and flying lemurs . Rodentia (rodents) Lagomorpha (rabbits, hares, pikas) Scandentia (treeshrews) Dermoptera (flying lemurs) Primates († Plesiadapiformes , Strepsirrhini , Haplorrhini ) Laboratory mice are the same species as the house mouse ; however, they are often very different in behaviour and physiology . There are hundreds of established inbred , outbred , and transgenic strains. A strain , in reference to rodents,

8512-490: The construction of enormously complex signaling networks. As interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types. The best-known role of proteins in

8624-408: The derivative unit kilodalton (kDa). The average size of a protein increases from Archaea to Bacteria to Eukaryote (283, 311, 438 residues and 31, 34, 49 kDa respectively) due to a bigger number of protein domains constituting proteins in higher organisms. For instance, yeast proteins are on average 466 amino acids long and 53 kDa in mass. The largest known proteins are the titins , a component of

8736-776: The design and execution of the tests themselves. In addition, the caging of laboratory animals may render them irrelevant models of human health because these animals lack day-to-day variations in experiences, agency, and challenges that they can overcome. The impoverished environments inside small mouse cages can have deleterious influences on biomedical results, especially with respect to studies of mental health and of systems that depend upon healthy psychological states. For example, researchers have found that many mice in laboratories are obese from excess food and minimal exercise, which alters their physiology and drug metabolism. Many laboratory animals, including mice, are chronically stressed, which can also negatively affect research outcomes and

8848-438: The dose of 100 mg per kg body weight) plus xylazine (in the dose of 5–10 mg per kg), injected by the intraperitoneal route. It has a duration of effect of about 30 minutes. Approved procedures for euthanasia of laboratory mice include compressed CO 2 gas, injectable barbiturate anesthetics , inhalable anesthetics, such as Halothane, and physical methods, such as cervical dislocation and decapitation. In 2013,

8960-486: The early 20th century. In 1902 Lucien Cuénot published the results of his experiments using mice which showed that Mendel's laws of inheritance were also valid for animals — results that were soon confirmed and extended to other species. In the early part of the 20th century, Harvard undergraduate Clarence Cook Little was conducting studies on mouse genetics in the laboratory of William Ernest Castle . Little and Castle collaborated closely with Abbie Lathrop who

9072-447: The erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed by Mulder's associate Berzelius; protein is derived from the Greek word πρώτειος ( proteios ), meaning "primary", "in the lead", or "standing in front", + -in . Mulder went on to identify the products of protein degradation such as

9184-472: The female does not mate during the postpartum estrus, she resumes cycling 2–5 days post-weaning. Newborn males are distinguished from newborn females by noting the greater anogenital distance and larger genital papilla in the male. This is best accomplished by lifting the tails of littermates and comparing perinea . Mice are mammals of the clade (a group consisting of an ancestor and all its descendants) Euarchontoglires , which means they are amongst

9296-399: The head, snout, and shoulders, although barbering may appear anywhere on the body. Also self-barbering can occure. Both hair and vibrissae may be removed. Barbering is more frequently seen in female mice; male mice are more likely to display dominance through fighting. C57BL/6 has several unusual characteristics which make it useful for some research studies but inappropriate for others: It

9408-503: The help of transgenic mouse models, researchers can make progress in AD research by understanding the intricate relationships between gene products that are involved in the production of Aβ peptide.e physiology and biochemistry of the illness. Traditionally, laboratory mice have been picked up by the base of the tail. However, recent research has shown that this type of handling increases anxiety and aversive behaviour. Instead, handling mice using

9520-525: The late 1700s and early 1800s included gluten , plant albumin , gliadin , and legumin . Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the Swedish chemist Jöns Jacob Berzelius in 1838. Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula , C 400 H 620 N 100 O 120 P 1 S 1 . He came to

9632-478: The major component of connective tissue, or keratin , the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane . A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration , are called dehydrons . Many proteins are composed of several protein domains , i.e. segments of

9744-399: The many available strains includes - Since 1998, it has been possible to clone mice from cells derived from adult animals. There are many strains of mice used in research, however, inbred strains are usually the animals of choice for most fields. Inbred mice are defined as being the product of at least 20 generations of brother X sister mating, with all individuals being derived from

9856-443: The mature mRNA, which is then used as a template for protein synthesis by the ribosome . In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid . In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm , where protein synthesis then takes place. The rate of protein synthesis

9968-405: The membranes of specialized B cells known as plasma cells . Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high. Many ligand transport proteins bind particular small biomolecules and transport them to other locations in

10080-559: The murine astrovirus was not known. In the U.K., as with all other vertebrates and some invertebrates, any scientific procedure which is likely to cause "pain, suffering, distress or lasting harm" is regulated by the Home Office under the Animals (Scientific Procedures) Act 1986 . U.K. regulations are considered amongst the most comprehensive and rigorous in the world. Detailed data on the use of laboratory mice (and other species) in research in

10192-496: The nobel prize in 1972, solidified the thermodynamic hypothesis of protein folding, according to which the folded form of a protein represents its free energy minimum. With the development of X-ray crystallography , it became possible to determine protein structures as well as their sequences. The first protein structures to be solved were hemoglobin by Max Perutz and myoglobin by John Kendrew , in 1958. The use of computers and increasing computing power also supported

10304-500: The order of 50,000 to 1 million. By contrast, eukaryotic cells are larger and thus contain much more protein. For instance, yeast cells have been estimated to contain about 50 million proteins and human cells on the order of 1 to 3 billion. The concentration of individual protein copies ranges from a few molecules per cell up to 20 million. Not all genes coding proteins are expressed in most cells and their number depends on, for example, cell type and external stimuli. For instance, of

10416-507: The overwhelming majority of studies, while the human population is heterogeneous, pointing to the importance of studies in interstrain hybrid, outbred , and nonlinear mice. An article in The Scientist notes, "The difficulties associated with using animal models for human disease result from the metabolic, anatomic, and cellular differences between humans and other creatures, but the problems go even deeper than that" including issues with

10528-409: The physical and behavioural characteristics of house mice; however, due to many generations of artificial selection, some of these characteristics now vary markedly. Due to the large number of strains of laboratory mice, it is impractical to comprehensively describe the appearance and behaviour of all of them; however, they are described below for two of the most commonly used strains. C57BL/6 mice have

10640-440: The physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Some proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors . Proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes . Once formed, proteins only exist for a certain period and are then degraded and recycled by

10752-424: The process of cell signaling and signal transduction . Some proteins, such as insulin , are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues . Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on

10864-534: The protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity. The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according to their charge using electrofocusing . For natural proteins,

10976-427: The proteins in the cytoskeleton , which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses , cell adhesion , and the cell cycle . In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized . Digestion breaks the proteins down for metabolic use. Proteins have been studied and recognized since

11088-743: The rodent analogues of DAF. and DAF-Fc has yet to be tested in humans. Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement mediated lysis. Protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues . Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions , DNA replication , responding to stimuli , providing structure to cells and organisms , and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which

11200-582: The same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein–protein interactions also regulate enzymatic activity, control progression through the cell cycle , and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows

11312-573: The sample, allowing scientists to obtain more information and analyze larger structures. Computational protein structure prediction of small protein structural domains has also helped researchers to approach atomic-level resolution of protein structures. As of April 2024 , the Protein Data Bank contains 181,018 X-ray, 19,809 EM and 12,697 NMR protein structures. Proteins are primarily classified by sequence and structure, although other classifications are commonly used. Especially for enzymes

11424-430: The sequencing of complex proteins. In 1999, Roger Kornberg succeeded in sequencing the highly complex structure of RNA polymerase using high intensity X-rays from synchrotrons . Since then, cryo-electron microscopy (cryo-EM) of large macromolecular assemblies has been developed. Cryo-EM uses protein samples that are frozen rather than crystals, and beams of electrons rather than X-rays. It causes less damage to

11536-408: The size of the human genome. Estimating the number of genes contained in the mouse genome is difficult, in part because the definition of a gene is still being debated and extended. The current count of primary coding genes in the laboratory mouse is 23,139. compared to an estimated 20,774 in humans. Various mutant strains of mice have been created by a number of methods. A small selection from

11648-405: The substrate, and an even smaller fraction—three to four residues on average—that are directly involved in catalysis. The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site . Dirigent proteins are members of a class of proteins that dictate the stereochemistry of a compound synthesized by other enzymes. Many proteins are involved in

11760-706: The surrounding amino acids may determine the exact binding specificity). Many such motifs has been collected in the Eukaryotic Linear Motif (ELM) database. Topology of a protein describes the entanglement of the backbone and the arrangement of contacts within the folded chain. Two theoretical frameworks of knot theory and Circuit topology have been applied to characterise protein topology. Being able to describe protein topology opens up new pathways for protein engineering and pharmaceutical development, and adds to our understanding of protein misfolding diseases such as neuromuscular disorders and cancer. Proteins are

11872-400: The tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain . Proteins are always biosynthesized from N-terminus to C-terminus . The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass , which is normally reported in units of daltons (synonymous with atomic mass units ), or

11984-472: The tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10 M) but does not bind at all to its amphibian homolog onconase (> 1 M). Extremely minor chemical changes such as

12096-640: The top 10 most popular strains according to Jackson Laboratories . The Jackson Labs DO ( Diversity Outbred ) project is a mouse breeding program using multiple inbred founder strains to create a genetically diverse population of mice for use in scientific research. These mice are designed for fine genetic mapping , and capture a large portion of the genetic diversity of the mouse genome. This project has resulted in over 1,000 genetically diverse mice which have been used to identify genetic factors for diseases such as obesity, cancer, diabetes, and alcohol use disorder. Laboratory mice have retained many of

12208-466: Was insulin , by Frederick Sanger , in 1949. Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids , or cyclols . He won the Nobel Prize for this achievement in 1958. Christian Anfinsen 's studies of the oxidative folding process of ribonuclease A, for which he won

12320-492: Was a breeder of fancy mice and rats which she marketed to rodent hobbyists and keepers of exotic pets, and later began selling in large numbers to scientific researchers. Together they generated the DBA (Dilute, Brown and non-Agouti) inbred mouse strain and initiated the systematic generation of inbred strains. The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of

12432-512: Was influential in promoting the mouse as a laboratory organism. In 2011, an estimated 83% of laboratory rodents supplied in the U.S. were C57BL/6 laboratory mice. Sequencing of the laboratory mouse genome was completed in late 2002 using the C57BL/6 strain. This was only the second mammalian genome to be sequenced after humans. The haploid genome is about three billion base pairs long (3,000 Mb distributed over 19 autosomal chromosomes plus 1 respectively 2 sex chromosomes), therefore equal to

12544-581: Was not fully appreciated until 1926, when James B. Sumner showed that the enzyme urease was in fact a protein. Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding , an idea first put forth by William Astbury in 1933. Later work by Walter Kauzmann on denaturation , based partly on previous studies by Kaj Linderstrøm-Lang , contributed an understanding of protein folding and structure mediated by hydrophobic interactions . The first protein to have its amino acid chain sequenced

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