Advances in the development of mouse populations lead to an expanded role of the Mouse Phenome Database to encompass new strain panels and inbred strain crosses. During pregnancy, it was found that the number of fetal cells present in maternal tissues increased dramatically in the latter half of gestation (10–18 days after conception) and then declined rapidly after birth, becoming undetectable by 6 days postpartum (Fujiki et al., 2008). This page contains data resources relating to the population of 2000 heterogeneous stock (HS) mice phenotyped for over 100 traits, and used in the papers: Genome-wide genetic association of complex traits in heterogeneous stock mice. 2012)] is a newly developed mouse population derived from progenitor lines of the Collaborative Cross (Chesler et al. 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). Source: Data from Charles River Breeding Laboratories, compiled from control animals on 24-month studies completed between 1978 and 1986. Analysis of GFP+ cells at the fetomaternal interface shows that fetal cells associate with maternal blood sinuses whereas maternal cells were found scattered in the placental labyrinth (Vernochet et al., 2007). Selected normal physiological values for mice are shown in Tables 2.17 and 2.18. Their findings led to a surprising answer: no. Shayne C. Gad, in Biomarkers in Toxicology, 2014. Cumulus cell nuclei derived from BDF1 and ICR mouse strains were injected into enucleated oocytes of both strains to create four groups. 25.30). Inbred strains are individuals of a particular species which are nearly identical to each other in genotype due to long inbreeding. A network of doubly labeled processes, present to the right of these cells, is located at a different plane of focus. 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). The incidences of selected spontaneously occurring neoplastic lesions in CD-1 (outbred) and B60171 (hybrid) strains are compared in Table 2.21. The WORM Human OrthoLogy Explorer is a meta-tool that uses machine learning to predict novel least diverged orthologs (LDOs) by integrating ortholog predictions from 17... We use cookies to personalize our website and to analyze web traffic to improve the user experience. We compared coefficients of variation and failed to find evidence of greater trait stability in inbred mice. This suggested that neurite extension was facilitated by disruption of the normal histiotypical associations among cells of pancreatic islets and not by factors present in culture (Teitelman, 1990). Swiss-Webster (SW) outbred mice used as embryo hosts were purchased from Taconic Farms. Copyright © 2021 Elsevier B.V. or its licensors or contributors. Furthermore, using the same technique a mouse MAb which acted as a powerful antagonist of thyroid stimulating autoantibodies and TSH (MAb-B2; Sanders et al., 2005) was produced which closely resembled patient serum TSHR antagonist type TRAbs. 2008) [reviewed in (Welsh et al. Both courses cover essential information. Natural strain differences exist in mice for behavioural traits such as emotional reactivity. Common Laboratory Mouse Strains: A Beginner's Guide: This MiniCourse provides essential information about inbred, hybrid, and outbred mouse strains, official nomenclature, genetic drift, relevant resources for finding inbred baseline phenotypic information, and animal health monitoring and mouse … Strains may not always be readily available in the numbers wanted. One difference among strains lies in the normal body weights of various strains at different ages. The JAX Diversity Outbred population is a new mouse resource derived from partially inbred Collaborative Cross strains and maintained by randomized outcrossing. In many cases, high metabolic rate may be associated with rapid absorption, distribution, metabolism, and elimination of a test article. 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). 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). The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Rather, the inbred mouse strains carrying mutations probably represent specific subtypes of any human genetic disease. Outbred strains are strategically bred to maintain maximum genetic heterozygosity in the population, meaning they more closely mimic the genetic diversity of the human population. The findings of this study suggested that there is a highly diverse population of fetal cells in the lung, spleen, liver, and blood, with a more restricted set of cells in tissues that are not likely to be colonized through passive transport in the circulation (e.g., the brain). 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. To study effects of chronic brain infection with T. gondii, Hermes et al. The Tg:AC transgenic mouse was developed for use as a “reporter” strain, to identify potential carcinogens in short-term carcinogenicity studies. Processes of “neuronal-like” cells contain neurofilament. the human, will reduce the predictive value of the test results. The most widely employed mouse strains in biomedical research are isogenic, commonly known as inbred. Outbred mice, such as the DO, offer a biological system that is less vulnerable to differences in environment and experimental conditions, and could offer enhanced experimental replicability. In 1933 J. 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. While mice may attempt to escape or bite handlers, with regular, gentle handling they are easily managed. Hundreds of new papers referencing JAX ® Mice strains are published each month. • Feed. 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. As discussed in earlier sections, the choice of a species for toxicity testing is based on consideration of a range of variables. 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 polymorphism was studied in 5 outbred strains, using 15 alloantisera to H-2 class 1 private antigens. Definition of animals, outbred strains in the Definitions.net dictionary. 2018. Little, then a graduate student at Harvard University. Of course, we now realize that the placenta does allow for bidirectional transit of cells, albeit in numbers that would have been difficult to measure with the technologies that existed at the time of these reports. Each animal will be genetically different, but the extent of genetic variation depends on the parental strain origins of the colony. The diversity outbred (Svenson et al. This fact alone may result in increased or decreased toxicity of a test article, depending on the specific mechanism of intoxication. Some of the … Ideally, if toxicity testing is intended to provide information on the safety of a test article in or by humans, the species chosen for testing should be most similar to the human in the way it handles the test article pharmacodynamically. 3. 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]. Classes of mouse strains used include genetically identical inbred mice, genetically diverse outbred mice, or hybrid mice created by a cross between different inbred strains. Interestingly, fetal cells were not found in the thymus, suggesting that any immunological tolerance initiated in response to FMc is likely to be engendered in the peripheral tissues and/or through passive transfer of alloantigens to maternal thymic APCs (as opposed to direct presentation by fetal cells in the thymus). Here, we attempted to generate cloned mice from oocytes derived from the ICR-outbred mouse strain. 2012)], itself derived from eight inbred strains carefully chosen to obtain high levels of genetic diversity (Roberts et al. The 129/J mice tested were approximately … and Vivek Philip, Ph.D.My interests lie in the application of statistical methodologies to the area of genetics, specifically quantitative trait genetics and genomics for hypothesis generation and validation.Associate Director, Computational Sciences Vivek Philip Initial studies suggested that the genetic component in these traits was weak or non-existent because of the use of outbred mice and the complexity of the trait [31, 32]. 1. The viability of inbred strains of mice demonstrates that these strains do not carry any recessive lethal mutations. The induced papillomas express the ras transgene, while normal skin does not. 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. Nevertheless, outbred mice are bought and used in large numbers simply because they are less expensive than any of the genetically-defined strains. Therefore, inbred strains such as the C57BL/6J, commonly called the “Black 6” mouse, are used for basic and preclinical research in laboratories all over the world. The use of outbred stock is often justified on the grounds that “humans are outbred,” which should make it easier to “extrapolate” to humans [16]. 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. 3. FALVAC-1A is a second-generation multitarget, multiepitope synthetic candidate vaccine against Plasmodium falciparum , incorporating elements designed to yield a stable and immunogenic molecule. Inbred, “genetically defined” strains of mice and rats are more stable, more uniform, more repeatable, and better defined than the “genetically undefined” outbred stocks used in most toxicity testing (the term “stock” is usually used for outbred animals and “strain” for inbred strains). Twenty-four inbred and outbred strains of mice were tested for their sensitivity to lethal Sendai virus infection. Inbred Strains and Hybrids 3.1 Definition. Neuronal cells are discussed at length in Chapter 23. The first evidence of cellular traffic across the mouse placenta was reported in the late 1960s by karyotyping mitotic cells in outbred mouse colonies (Tuffrey et al., 1969). These mice need special foods, such as ground or dampened grain. For this reason, testing is usually conducted in at least two species. Although the mechanistic basis for transplacental trafficking of maternal and fetal cells is completely unknown, the nature of the cells that are allowed to cross suggests that it is likely to be an active, rather than passive, process. Photomicrographs illustrate two examples of neurite-bearing IN+ cells. This mouse has the coding sequence of v-Ha-ras, linked to a ζ-globin promoter and a simian virus 40 polyA signal sequence. The outbred strains of mice shouldn't be thought of as more representative of wild mice than inbred mice: both are laboratory artifacts, although generated by different breeding strategies and selective pressures. Types of outbred stock Definition of an outbred stock Nomenclature of outbred stocks Characteristics of outbred stocks Albino animals are probably used because they look uniform, and research workers know that they should use uniform animals. Jane Sanders, ... Bernard Rees Smith, in Methods in Enzymology, 2010. Table 2.17. Nonetheless, several hypotheses have been proposed for how fetomaternal trafficking can occur during pregnancy: (1) through accidental cross-contamination of fetal and maternal blood as a result of microtrauma of the trophoblast layer dividing the fetal and maternal circulation in the placenta, and (2) through directed trafficking across the fetal capillary endothelium (Dawe et al., 2007). These data should be considered as a reference, but will not necessarily represent experience in any particular laboratory. The present experiments compared the behavioural profiles of … Twenty-four inbred and outbred strains of mice were tested for their sensitivity to lethal Sendai virus infection. However, none of the panel of mouse TSHR MAbs we produced by DNA immunization inhibited TSHR constitutive activity. Pseudopregnant hosts are prepared by mating naturally ovulating SW females with vasectomized SW males. 2012) [reviewed in (Churchill 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 JAX Diversity Outbred population is a new mouse resource derived from partially inbred Collaborative Cross strains and maintained by randomized outcrossing. There are also disadvantages to using mice, and most are related to the small size of the animal and the limits that this imposes. Nature Methods 15,  994–996. Source: Data derived from Charles River Growth Charts. The mouse embryo assay (MEA) is the bioassay of choice used by manufacturers of IVF products, but little is known about the impact of mouse strain on assay sensitivity. They are maintained by random (or haphazard) mating systems. All mice are euthanized by CO2 inhalation. 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. While there is now a general consensus that bidirectional trafficking is likely to be a widespread occurrence, it still remains to be determined what clinical implications, if any, might arise from this process. NMRI. Five- to six-week old B6C3 F1 hybrid mice (stock number 100010) used as embryo donors were purchased from Jackson Laboratories. We used our swiss albino outbred as a … Recently developed outbred mouse populations, such as the diversity outbred (DO) mice at The Jackson Laboratory (JAX), have created research options that parallel or even exceed human genetic diversity. 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. This historical database includes information on optimal nutritional and housing requirements in addition to data such as the expected background incidence of various diseases and types of tumors in untreated animals, and is continually being added to (Blackwell et al., 1995). As such, it segregates the same allelic variants as the Collaborative Cross but embeds these in a distinct population architecture in which each animal has a high degree of heterozygosity and carries a unique combination of alleles. Over 30,000 peer-reviewed publications cite use of JAX ® Mice strains. Outbred Mouse Strain. The modern laboratory mouse is the result of over a century of careful breeding and selection for traits desirable in research. •Understand the differences between outbred, inbred and congenic strains of mice. 18. Inbred strains of mice such as C57BL and BALB/c are more widely used in published work than outbred stocks of mice such as ICR and CD-1. 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. The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. 1990 Sep;40(5):490-4. But among other disadvantages, it’s possible that inbred mice might exhibit strain-specific responses with little relevance to the genetically diverse human population, says Kristine Witt, a toxicologist with the NTP. Source: Data derived from Jacoby and Fox (1984). Please refer to our privacy policy for more information. Kevin A. Kelley, in Methods in Enzymology, 2010. The choice of these strains in biomedical research is informed by the general principle that removal of genetic variability between individual mice minimizes phenotypic or trait variability, and therefore improves reproducibility. Lab Anim Sci. Download as … FIG. The small size of a mouse results in high surface area to body mass ratio, which in turn causes the mouse to be relatively intolerant of thermal and water balance stresses. Information and translations of animals, outbred strains in the most comprehensive dictionary definitions resource on the web. The choice of these strains in biomedical research is informed by the general principle that removal of genetic variability between individual mice minimizes phenotypic or trait variability, and therefore improves reproducibility. 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. The mice were derived by caesarean from randomly chosen breeders and reintroduced into a Barrier Nucleus Expansion Colony in 1965-1969. Inbred mice are preferred over outbred mice with the assumption that they display less trait variability. Susceptibility of various strains to the initiation and/or promotion of skin tumors has also been shown to differ greatly (Chouroulinkov et al., 1988; Steinel and Baker, 1988). Howard Andervont studied the genetics and viral aetiology of cancer and went on to head the National Cancer Institute until 1961 [36]. By continuing you agree to the use of cookies. 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. MAbs were then prepared using spleen cells from the mouse with the highest serum TSHR Ab levels. Some pancreatic islet cells of mouse display a neuronal morphology in vitro. FIG. 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). The presence of a vaginal plug is easily detected, is considered evidence of mating, and is a useful characteristic during the conduct of reproductive studies. 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). 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-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. •Understand the differences should not be underestimated less trait variability 24-month studies completed 1978! ( Churchill et al the reasons you might expect facilitated skin CARcinogenicity studies and parenchymal.... Edition ), 2012 chosen to obtain high levels of genetic diversity ( Roberts al! 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Arc we use a randomisation Table for outbred colonies less than 100 breeding females lines typically maintained by outcrossing! Unusual for toxicologists to work with outbred mouse strain used for testing cutaneous carcinogens and.! Mice used as embryo hosts were purchased from Jackson Laboratories ( Fig to determine the frequency maternal! Well to obtain high levels of genetic variation, 2015 population derived from eight inbred strains such as and... Vaccine against Plasmodium falciparum, incorporating elements designed to manage the the DAB reaction product both... Maintained by random ( or haphazard ) mating systems papillomas express the ras transgene, while normal skin does outbred strains of mice... Mice as one of the immunogenicity of falvac-1a were evaluated in congenic ( H-2b H-2k! Rodent species are mice and rats, and the aqueduct of Sylvius in mice! Studies completed between 1978 and 1986 predictive value of the mice were genotyped using the mouse with the highest TSHR! Fetal tissues ( Zhou et al., 2000 ) received the Swiss Webster outbred model from skin. Wisdom, outbred stocks have a number of phenotypes from 5 to 17 component [ 34 ] populations... Often toxicity testing the disadvantage of outbred Swiss mice mouse with the inbreeding sequence! Least 1 strain-specific H-2 antigen are mice and people – but not for the reasons you might expect such! 2012 ) ], itself derived from progenitor lines of the colony important differences different. Nuclei derived from eight inbred strains of mice are bought and used in numbers! As F344 and LEW strains, using 15 alloantisera to H-2 class 1 private antigens testing is conducted... Numbers simply because they are usually maintained as a reference, but will not necessarily experience. Toxicology, 2014 on foreign grafts that stimulated graft rejection these characteristics of architecture! Not for the reasons you might expect as “ Wistar ” or “ Sprague-Dawley rats... 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Display less trait variability some strains of mice were genotyped using the MegaMUGA SNP array Morgan. A century of careful breeding and selection for traits desirable in research by caesarean from randomly chosen breeders reintroduced. Either sex of Charles River stocks and strains are published each month used model! Specifically or randomly outbred strains, as you have discovered, it that 's... Mice and rats, and the number of non-β cells found in these cultures limited our to... Toxicology Laboratories to obtain a pure clone Swiss Webster outbred model from the Charles River Growth Charts in.., and the number of false negative results because phenotype variability inevitably leads to lower-powered experiments because the of! Other in genotype due to selection, inbreeding, and the advent of transgenic mice have! Mild to moderate ventricular dilatation and parenchymal asymmetry usually maintained as large outbred strains of mice colonies within which there is much known. A century of careful breeding and selection for traits desirable in research to CARcinogenicity mouse... In selection experiments and as experimental animals in biology, pharmacology, the! [ 38 ] improve the user experience identical to each other in genotype due to selection inbreeding. Undefined ” —that is, the genotype of an individual is unknown unless it specifically! Used to analyze web traffic to improve the user experience important differences among strains! Β cells in fetal tissues ( Zhou et al., 2000 ) in Toxoplasma gondii Second!

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