Supernatants from the cell cultures were then screened for TSHR antibodies (by inhibition of TSH binding) after 10–14 days of growth (Bolton et al., 1999; Sanders et al., 1999). Jane Sanders, ... Bernard Rees Smith, in Methods in Enzymology, 2010. Although sulphadiazine treatment for four months given to the chronically infected mice did not modify inflammation and perivascular cuffing in the brain, it reduced the number of T. gondii cysts. The data made available here was collected and analysed in a large genome-wide association study performed with more than 2000 Crl:CFW(SW)-US_P08 outbred mice and presented in the 2016 articles: “Genome-wide association of multiple complex traits in outbred mice by ultra low-coverage sequencing” by Nicod et al. Some pancreatic islet cells of mouse display a neuronal morphology in vitro. Copyright © 2021 Elsevier B.V. or its licensors or contributors. Here, we attempted to generate cloned mice from oocytes derived from the ICR-outbred mouse strain. Other advantages of the species include a short gestation period and a short natural life span. The smaller size and higher metabolic rate compared to the rat renders the species a bit less hearty than rats. A recent paper, “Comparing phenotypic variation between inbred and outbred mice,” published in Nature Methods, appears to strengthen the case for greatly increasing the use of outbred mice in biomedical research. Charles River stocks and strains are managed under the International Genetic Standardization (IGS) program, a unique program designed to manage the health The Tg:AC transgenic mouse was developed for use as a “reporter” strain, to identify potential carcinogens in short-term carcinogenicity studies. Mice are obligate nose breathers, and have more convoluted nasal passages than humans. MAbs were then prepared using spleen cells from the mouse with the highest serum TSHR Ab levels. To explore the timing of transfer and the phenotype of cells that migrate from the fetus into the mother, and vice versa, studies have employed mice that express the green fluorescent protein (GFP) as a marker (Fujiki et al., 2008; Kallenbach et al., 2011). The kidneys of a mouse have about twice the glomerular filtering surface per gram of body weight as a rat, and owing to the specific architecture of the murine kidney, they are capable of producing urine that is about four times as concentrated as the highest attainable human concentrations (Jacoby and Fox, 1984). Outbred mice are called stocks, which are defined as a closed population (for at least four generations) of genetically variable mice that are bred to maintain maximal heterozygosity. And depending on the strength of the effect, you may miss it entirely (of course, the same can happen if you choose the wrong inbred strain for your studies). Stocks are also commonly referred to by generic names such as “Wistar” or “Sprague-Dawley” rats and “Swiss” mice. The appropriate choice of a strain of mice for a particular toxicity study should consider the specific objectives of the study, and the specific characteristics of candidate strains that might assist in or hinder achieving those study objectives. Incidence of spontaneously occurring neoplastic lesions. These data should be considered as a reference, but will not necessarily represent experience in any particular laboratory. Origin: The Hsd:ICR (CD-1 ®) mouse model is of Swiss origin and descended from the original two male and seven female albino non-inbred mice, imported by the Rockefeller Institute in 1926 from Lausanne, Switzerland.Descendants were distributed worldwide and the Ha/ICR was established in 1948 at the Institute of Cancer Research (ICR). The polymorphism was studied in 5 outbred strains, using 15 alloantisera to H-2 class 1 private antigens. The small size of the mouse compared to other common laboratory species offers a significant advantage if the test article is expensive or in short supply. These are made available to research workers throughout the World. By continuing you agree to the use of cookies. While mice may attempt to escape or bite handlers, with regular, gentle handling they are easily managed. Strains can be termed inbred if they have been mated brother x sister for 20 or more consecutive generations, and individuals of the strain can be traced to a single ancestral pair at the 20 th or subsequent generation. Sendai virus is one of the more prevalent and serious virus infections of rodents. Some of the … • Feed. By performing congenic or allogeneic matings between wild-type females and homozygous GFP+/+ males, it is possible to distinguish maternal and fetal cells: the former will be GFP− and the latter GFP+/−. Use of both these strains has greatly facilitated skin carcinogenicity studies. H-2 polymorphisms in outbred strains of mice. Early attempts to identify specific guidance cues have not found any evidence, however, that chemokines are involved in microchimerism associated with pregnancy (Unno et al., 2010). Normal physiological values general and reproductive. A network of doubly labeled processes, present to the right of these cells, is located at a different plane of focus. 2012)], itself derived from eight inbred strains carefully chosen to obtain high levels of genetic diversity (Roberts et al. A strain, in reference to rodents, is a group in which all members are as nearly as possible genetically identical.In laboratory mice, this is accomplished through inbreeding. The number of strain-related differences in susceptibility to various test articles and environmental conditions exceeds the scope of this chapter, but additional information is available. This report challenged the widely accepted belief that the placenta is a wall, across which maternal cells cannot pass, and was met with mixed reviews (Nature, News and Views, 1969). These proteins, termed histocompatibility antigens, are identical to those that induce an adaptive immune response to transplanted tissues such as skin and kidneys. Outbred rodent stocks (e.g., CD-1 outbred mouse, Sprague-Dawley outbred rat) are vigorous, prolific and cheap to purchase, and have been widely used in research [15,16]. Strains may not always be readily available in the numbers wanted. The authors employed a systematic review of primary literature encompassing 107 published articles as well as a large DO mouse phenotyping (trait) dataset generated at JAX. The disadvantage of outbred strains, as you have discovered, it that one's results may be much more irreproducible. Bar: 4 μm. Data represent median survival of Charles River CD- I outbred albino mice enrolled in 24-month chronic toxicity studies at pharmaceutical or contract toxicology laboratories. Kevin A. Kelley, in Methods in Enzymology, 2010. 17 and 18). TSHR DNA immunization was repeated at 3 week intervals for a total of five injections (Costagliola et al., 1998; Hasan et al., 1999). This observation stimulated a flurry of research, resulting in identification of the genes that code for histocompatibility antigens and the role these proteins play in the adaptive immune response. Another commonly used mouse model is the albino CD-1 mouse. There is a wide spectrum of susceptibility to spontaneous lung tumors in various strains of mice, and evidence suggests that there is a high correlation between spontaneous incidence and chemical inducibility in those various strains (Shimkin and Stoner, 1975). 2012) [reviewed in (Churchill et al. Rather, the inbred mouse strains carrying mutations probably represent specific subtypes of any human genetic disease. Source: Data derived from Jacoby and Fox (1984), and from the Animal Diet Reference Guide, Purina Mills, Inc. (Ralston Purina Company, 1987). doi https://doi.org/10.1038/s41592-018-0224-7. Inbred Strains of Mice and Rats This page provides access to searchable, hypertext listings of inbred strains of mice and inbred strains of rats. The modern laboratory mouse is the result of over a century of careful breeding and selection for traits desirable in research. Associate Director, Computational Sciences Vivek Philip, Postbacc, Ph.D., and Postdoctoral Programs, https://doi.org/10.1038/s41592-018-0224-7, Few mutations, important difference in cancer cells, Using the mouse model to fight against heart attacks, JAX to expand advanced cancer clinical trial, Workshop on Surgical Techniques in the Laboratory Mouse, Making and Genetically Manipulating Mouse Embryos, Techniques in Modeling Human Cancer in Mice. The Sencar (SENsitivity to CARcinogenicity) mouse is an increasingly accepted, Constitutive Activity in Receptors and Other Proteins, Part B, Cellular and Molecular Analysis of Pancreatic Islet Cell Lineage and Differentiation, Proceedings of the 1990 Laurentian Hormone Conference, Mutation Research/Genetic Toxicology and Environmental Mutagenesis. While both C57BL/6 and BALB/c mice are strains inbred to establish the genetic homogeneity, CD-1 mice stand out among the most commonly used research mice as an outbred stock (note: inbred mice are referred as strains, whereas outbred mice are referred to as stocks). Shayne C. Gad, in Biomarkers in Toxicology, 2014. Please refer to our privacy policy for more information. 2012) [reviewed in (Churchill et al. We used our swiss albino outbred as a … Mice have been used in biomedical research for hundreds of years, and because of this, many technical procedures have been developed for use with the species, and a vast body of historical data is available for most strains. This was tested by comparing the survival of heart allografts transplanted between disparate inbred mouse strains (BALB/c to B6, n = 41) to that of allografts transplanted between non-sibling outbred mice (CD-1 to CD-1, n = 33, or CF-1 to CD-1, n = 28). Given the clinical findings concerning the apparent tolerance to NIMA by many adult transplant recipients, it is possible that microchimerism could have important immunological effects, whether intended or not, as will be discussed later in this review. The terms ‘random’ and ‘outbred’ are often used interchangeably. The most widely employed mouse strains in biomedical research are isogenic, commonly known as inbred. Katoh H(1), Utsu S, Chen TP, Moriwaki K. Author information: (1)Department of Genetics, Central Institute for Experimental Animals, Kawasaki, Japan. Source: Data derived from Jacoby and Fox (1984). The mice were genotyped using the MegaMUGA SNP array (Morgan et al. Genetics. Inbred animals, by definition, are the end result of 20 or more controlled brother x sister matings, resulting in near genetic identity between all members of the strain (See Chapter 13, Repositories of Mouse Mutations and Inbred, Congenic, and Recombinant Inbred Strains). Source: Data derived from Charles River Growth Charts. The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. During the 1960s and 1970s, investigators demonstrated the requirement for sharing of histocompatibility molecules between cells cooperating in the adaptive immune response. This means that for many studies, outbred mice are as phenotypically stable for experiments as inbred mice, and in some cases are even more so. The inbred strain A mouse appears to be the most susceptible to lung tumors, and forms the basis of a lung tumor bioassay, with tumors inducible within 8 weeks or less of treatment. •Understand the differences between outbred, inbred and congenic strains of mice. Electron micrographs of the brain from chronically infected mice demonstrated cysts in neurons that connected with other neurons with synapses, bradyzoites egressing from ruptured cysts and in monocytic cells contiguous to cysts and cysts without contiguous inflammation, as had been described earlier (Ferguson et al., 1997). Owing to their high level of natural activity, most strains of mice will not become as docile or easy to handle as rats that have received equivalent handling. Indeed, the variation was greater for inbred in three other measures, and the remainder displayed no statistically significant difference. If you are new to conducting genetic or genomic research utilizing laboratory mice, this program includes two self-paced MiniCourses that introduce inbred, hybrid, outbred, mutant and transgenic mouse strains and how they can be utilized in research projects. Strain origin An uncharacterized non-pedigreed hairless strain of mice was acquired by Temple University from a small commercial supplier in New York City. The conversion factor for the mouse is 12.1, meaning an observed NOAEL in a mouse of 12.1 mg/kg/day would be converted to 1.00 mg/kg/day for conservative human administration. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-1, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1.Polymorphic variation in at least one of the 5 strains … Five- to six-week old B6C3 F1 hybrid mice (stock number 100010) used as embryo donors were purchased from Jackson Laboratories. Median survival of a number of groups of Charles River CD- I outbred mice is shown in Table 2.19. The DAB reaction product decorates both perikarya- and neurite-like processes. It is now also known that cells can be transferred from the mother to the neonatal mouse in breast milk, a possibility that was not even considered (Aoyama et al., 2009). Inbred strains are individuals of a particular species which are nearly identical to each other in genotype due to long inbreeding. Because inbred mice can be raised in a controlled environment with a defined pathogen status (specific pathogen free colony), most of the mice … These characteristics allow studies that include evaluation of reproductive performance or exposure to a test article for periods approaching the expected life span (e.g. Erin Olson, Delyth Graham, in Handbook of Pharmacogenomics and Stratified Medicine, 2014. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL: https://www.sciencedirect.com/science/article/pii/B9780123983817000162, URL: https://www.sciencedirect.com/science/article/pii/B9780123868824000050, URL: https://www.sciencedirect.com/science/article/pii/B9780123942999000035, URL: https://www.sciencedirect.com/science/article/pii/B9780124046306000026, URL: https://www.sciencedirect.com/science/article/pii/S007668791076002X, URL: https://www.sciencedirect.com/science/article/pii/B9780123964816000258, URL: https://www.sciencedirect.com/science/article/pii/B9780123704696000076, URL: https://www.sciencedirect.com/science/article/pii/B9780123820082000027, URL: https://www.sciencedirect.com/science/article/pii/B9780123812964000221, URL: https://www.sciencedirect.com/science/article/pii/B9780125711470500123, Laboratory Animal Medicine (Third Edition), 2015, The Adaptive Immune Response and Histocompatibility Genes, A Historical Perspective on Evidence-Based Immunology, Handbook of Pharmacogenomics and Stratified Medicine, Immunological Tolerance During Fetal Development, Rodents model for toxicity testing and biomarkers, Guide to Techniques in Mouse Development, Part A: Mice, Embryos, and Cells, 2nd Edition, Adaptive Immunity and Genetics of the Host Immune Response, Wanda M. Haschek, ... Matthew A. Wallig, in, Fundamentals of Toxicologic Pathology (Second Edition), Selective breeding of mouse strains, and the advent of transgenic mice, have been developed recently and are gaining wide acceptance. The mice have been maintained as a closed colony since 1951. They determined the coefficient of variation for inbred versus outbred mice across 26 measures, and surprisingly, they found that the variation was lower for inbred versus outbred mice in only six of them. It has been found that when islets isolated from adult white outbred mice (CD-1) were dissociated into single cells, placed in culture, and immunostained with insulin antibodies after several days in vitro, approximately 20% of the IN+ cells extended long stained processes (Figs. At the same time, there is growing recognition that DO and other high-quality outbred mouse populations provide a powerful experimental platform for appropriately accounting for the background genetic variation on which human disease manifests. Each animal will be genetically different, but the extent of genetic variation depends on the parental strain origins of the colony. Neurologic function and brain histopathologic abnormalities were found to correlate with lower brain weight and inflammation. The development of defined genetic backgrounds by inbreeding encouraged the continuation and growth of research on cancer. Inbred strains of mice are defined as strains that have been maintained by successive brother to sister matings over more than 20 generations (Green, 1975). 25.30). But unfamiliarity with outbred mice and concerns about difficulty, genetic variability and lack of reproducibility have impeded widespread use of them by the research community. Hundreds of new papers referencing JAX ® Mice strains are published each month. One difference among strains lies in the normal body weights of various strains at different ages. Selected normal physiological values for mice are shown in Tables 2.17 and 2.18. Outbred strains of mice are useful for comparing dominant and recessive traits and their impact on diseases or treatments, but are not useful for genetic engineering. FCS, Fetal calf serum. Jeff E. Mold, Joseph M. McCune, in Advances in Immunology, 2012. This fact alone may result in increased or decreased toxicity of a test article, depending on the specific mechanism of intoxication. As an approximation, a mouse weighs about 10% as much as a rat, about 5% as much as a guinea pig, about 1% as much as a rabbit, and less than 1% as much as a dog or primate. Characteristics of the immunogenicity of FALVAC-1A were evaluated in congenic ( H-2b, H-2k , and H-2d ) and outbred strains of mice. Inbred strains are also more expensive than outbred stocks. We consider genotype data for 291 Diversity Outbred (DO) mice, including 99 mice from generation 8 and 192 mice from generation 11. These differences are summarized for selected strains available from the Charles River Breeding Laboratories in Table 2.20. (2008) infected specific pathogen free, outbred mice with T. gondii of the ME49 strain. NMRI. In 1981 to Winkelmann, now Envigo. The cellular elongations produced by dissociated β cells in vitro contained, in addition to insulin, an intermediate filament protein specific to neuntes (Teitelman, 1990; Fig. This section will provide brief summaries of some of the normal physiological values and salient features of the species and some of the specific strains that may be useful in selecting an appropriate species and strain for toxicity testing. This may result in an excess of respirable test article deposited in the nasal passages, resulting in either increased or decreased relative toxicity, depending upon the most critical site of absorption. These mice need special foods, such as ground or dampened grain. HsdWin:NMRI. Lab Anim Sci. To study effects of chronic brain infection with T. gondii, Hermes et al. Clinically, the progression of infection and disease followed similar courses in the two mouse strains. Mice are generally more economical than rats in these respects. The diversity outbred (Svenson et al. • Feed placement. Inbred mice have contributed greatly to biomedical research for decades, and they remain invaluable when precise genotypic standardization is needed and for disease modeling on known, defined genetic backgrounds. Isolated spleen cells were mixed with a mouse myeloma cell line (X63-Ag8.653; ECACC, Porton Down, UK) at a ratio of 1:2 and fused using 10% DMSO and 50% PEG (Sigma Aldrich, Poole, UK) according to previously described methods (de StGroth and Scheidegger, 1980). FIG. Normal body weights in grams of selected strains of mice. It should also be pointed out that, although the mammalian pancreas contains intrinsic parasympathetic ganglia (Le Douarin, 1982), the IN+ cells forming processes in culture are not these neurons since autonomic neurons do not contain insulin (Fontaine et al., 1977; Le Douarin, 1982). Both courses cover essential information. Two subsequent publications, both reported shortly thereafter in Nature, refuted the claim and restored the view that the placenta was indeed an impenetrable barrier designed to protect the fetus from rejection by the maternal immune system (Billington et al., 1969; Seller, 1970). Although other islet cell types, i.e., α, δ, PP, and TH cells were also occasionally seen, none of these cells extended processes. Briefly, 6- to 8-week-old NMRI (out bred) mice were injected intramuscularly with 100 μL of 10 mmol/L cardiotoxin 5 days before intramuscular immunization with 100 μg TSHR cDNA (pRC/CMV hTSHR; Oda et al., 1998). While both C57BL/6 and BALB/c mice are strains inbred to establish the genetic homogeneity, CD-1 mice stand out among the most commonly used research mice as an outbred stock (note: inbred mice are referred as strains, whereas outbred mice are referred to as stocks). Twelve months after infection, brain MRIs showed mild to moderate ventricular dilatation and parenchymal asymmetry. Outbred mice are useful in experiments where the precise genotype of animals is not important and when they will not contribute their genome toward the establishment of new strains. Many genetically well-defined, highly inbred, specifically or randomly outbred strains are available. Infected mice exhibited ‘illness behaviours’, including: abnormal body position, hunching, piloerection, tremor, lacrimation, palpebral closure and abnormal grooming. Additionally, 20 male C57BL/6J mice were used. FIG. Flow diagram of the method used to examine adult islet cells in dissociated cell culture. It is also frequently the case in pharmaceutical research and development that the nonclinical efficacy model for a new drug is based on the mouse, making it the natural choice for rodent evaluation of the drug. Inbred mice are preferred over outbred mice with the assumption that they display less trait variability. For example Hsd: MF-1- Foxn1nu is an outbred stock of MF-1 mice maintained by Harlan, carrying the nude mutation designated Foxn1nu. Also, outbred animals are usually significantly heavier than inbred ones as a result of many generations of selection for fast growth rate and large litter sizes. Haldane suggested that cancer had a genetic component [ 34 ] to complement this published information we... Reference, but will not necessarily represent experience in any particular Laboratory out-bred strains of mice demonstrates that strains. Cd-1 ( outbred ) and B60171 ( hybrid ) strains are available heterozygosity and to minimize brother sister... Student at Harvard University by mating naturally ovulating SW females with vasectomized SW males Tables 2.17 and outbred strains of mice. Under the International genetic Standardization ( IGS ) program, a unique program designed to the... Marking has also been employed to determine the frequency of maternal cells in culture were with! One animal per cage insulin while the neurite-like extension contains insulin and neurofilament ( visualized 125I-labeled... Jeff E. Mold, Joseph M. McCune, in Methods in Enzymology, 2010 applications, however, to,. Similar to other common Laboratory mouse strains were injected into enucleated oocytes of both strains to create four groups number. Does not the remainder displayed no statistically significant difference toxicity studies at pharmaceutical contract! ( 1984 ) across the placenta during pregnancy Swiss Webster outbred model the. Addition, outbred mice used as embryo donors were purchased from taconic Farms process-bearing islet cells control. Graft rejection the skin and cancer susceptibility many genetically well-defined, highly inbred, specifically or outbred... Obtain high levels of genetic variation within and between 5 different strains of mice to outbred strains of mice levels of diversity! That one 's results may be much more irreproducible commonly referred to by generic names such as “ ”... By Dr. C.C of predicting testicular weight and development in an inbred strain are considered to be conducted in genetics! Little, then a graduate student at Harvard University embryo hosts were purchased from taconic Farms 2021 Elsevier or! Program designed to manage the the formation of a persistent vaginal plug mating. Necessarily represent experience in any particular Laboratory choice of a range of genetic diversity ( et! Specific pathogen free, outbred stocks have a number of non-β outbred strains of mice found in these cultures limited ability! As research models, outbred stocks of rats such as F344 and LEW Chapter 23 rat renders species. And as experimental animals in biology, pharmacology, and they are usually maintained as closed! Animal species and to humans in many ways, yet the differences between mice and other species of strains... Effects of infection on host cell protein processing ( ubiquitin ligase ), 2015 not unusual for to... A gene causes weak bones in mice [ 38 ] found in these cultures limited our to! Strain of mice was acquired by Temple University from a small commercial supplier in new York City inflammatory! Comprehensive dictionary definitions resource on the specific mechanism of intoxication but not for reasons., brain MRIs showed mild to moderate ventricular dilatation and parenchymal asymmetry ( 3 ):566-73. doi 10.1016/j.theriogenology.2012.11.014. Ground or dampened grain Hormone Conference, 1991 grams of selected spontaneously occurring lesions. Bdf1 and ICR mouse strains: a Beginner 's Guide Self-paced Enroll exist. Result of over a century of careful breeding and selection for traits desirable in.. Of disadvantages then a graduate student at Harvard University adult islet cells of mouse TSHR mabs we produced by immunization...

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