Skin Grafting and The Homogeneity of Inbred Mouse Strains

Summary The results of the routine skin grafting on mice from fifteen inbred strains have been collated and examined. It has been shown that when strains are maintained on a modification of the single line breeding system there is an overall frequency of only two per cent of graft rejections with at least six generations between donor and recipient mice. Successful grafts are usually obtained even when donor and recipient mice are separated by as many as fourteen generations. It is suggested that mice not more than two generations from their common ancestor should be used for large scale skin grafting experiments because of the unsuccessful skin transfer between some mice more distantly related. With some mouse strains difficulty of graft healing is apparent, and it has been shown that these results point to a valid difference between the C57 and A strains.

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Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains

Physiological Genomics ◽

10.1152/physiolgenomics.00071.2010 ◽

2010 ◽

Vol 42A (2) ◽

pp. 103-113 ◽

Cited By ~ 54

Author(s):

Matthew S. Barnabei ◽

Nathan J. Palpant ◽

Joseph M. Metzger

Keyword(s):

Cardiac Function ◽

Genetic Divergence ◽

Ex Vivo ◽

Inbred Mouse ◽

Critical Role ◽

Inbred Strains ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Cardiac Decompensation

Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.

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Large-scale, high-throughput screening for coagulation and hematologic phenotypes in mice*

Physiological Genomics ◽

10.1152/physiolgenomics.00077.2002 ◽

2002 ◽

Vol 11 (3) ◽

pp. 185-193 ◽

Cited By ~ 52

Author(s):

Luanne L. Peters ◽

Eleanor M. Cheever ◽

Heather R. Ellis ◽

Phyllis A. Magnani ◽

Karen L. Svenson ◽

...

Keyword(s):

High Throughput ◽

High Throughput Screening ◽

Large Scale ◽

Inbred Mouse ◽

Inbred Strains ◽

Sample Volume ◽

Small Sample ◽

Mouse Strains ◽

Phenotypic Data ◽

Multiple Tests

The Mouse Phenome Project is an international effort to systematically gather phenotypic data for a defined set of inbred mouse strains. For such large-scale projects the development of high-throughput screening protocols that allow multiple tests to be performed on a single mouse is essential. Here we report hematologic and coagulation data for more than 30 inbred strains. Complete blood counts were performed using an Advia 120 analyzer. For coagulation testing, we successfully adapted the Dade Behring BCS automated coagulation analyzer for use in mice by lowering sample and reagent volume requirements. Seven automated assay procedures were developed. Small sample volume requirements make it possible to perform multiple tests on a single animal without euthanasia, while reductions in reagent volume requirements reduce costs. The data show that considerable variation in many basic hematological and coagulation parameters exists among the inbred strains. These data, freely available on the World Wide Web, allow investigators to knowledgeably select the most appropriate strain(s) to meet their individual study designs and goals.

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Hydronephrosis in inbred strains of mice with particular reference to the BRVR strain

Laboratory Animals ◽

10.1258/002367773780944067 ◽

1973 ◽

Vol 7 (3) ◽

pp. 229-236 ◽

Cited By ~ 10

Author(s):

D. M. Taylor ◽

H. Fraser

Keyword(s):

Inbred Mouse ◽

Inbred Strains ◽

The Other ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Concomitant Infection ◽

Inbred Strains Of Mice ◽

Dietary Variation

Hydronephrosis occurred in 6 of the 13 inbred mouse strains maintained in the same colony. Its incidence was high only in the BRVR strain, where about half of the cases could only be detected microscopically. There was no concomitant infection even in severely abnormal BRVR kidneys and the incidence of the condition was not influenced by dietary variation. The hydronephrosis found, less frequently, in 5 of the other strains was of a different type from that in BRVR mice.

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A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild-derived and classical inbred mouse strains

10.1101/631754 ◽

2019 ◽

Author(s):

Corey T. Watson ◽

Justin T. Kos ◽

William S. Gibson ◽

Leah Newman ◽

Gintaras Deikus ◽

...

Keyword(s):

High Throughput Sequencing ◽

Inbred Mouse ◽

Disease Model ◽

Inbred Strains ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Strain Variation ◽

In The Wild ◽

Model Strain ◽

Novel Allele

ABSTRACTThe genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic diversity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflect differences in subspecies origin. To investigate this hypothesis, we conducted high-throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ), and diversity (IGHD) genes in four inbred wild-derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ, and PWD/PhJ), and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild-derived strains, including 247 not curated in the International Immunogenetics Information System. In contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. In contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of diversity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand inter-strain variation in models of antibody-mediated disease.

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Analysis of Structural Variation Among Inbred Mouse Strains Identifies Genetic Factors for Autism-Related Traits

10.1101/2021.02.18.431863 ◽

2021 ◽

Author(s):

Ahmed Arslan ◽

Zhuoqing Fang ◽

Meiyue Wang ◽

Zhuanfen Cheng ◽

Boyoung Yoo ◽

...

Keyword(s):

Genetic Factors ◽

Sequence Data ◽

Inbred Mouse ◽

Inbred Strains ◽

Autism Spectrum ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Genetic Traits ◽

Long Read ◽

Short Read Sequence

AbstractThe genomes of six inbred strains were analyzed using long read (LR) sequencing. The results revealed that structural variants (SV) were very abundant within the genome of inbred mouse strains (4.8 per gene), which indicates that they could impact genetic traits. Analysis of the relationship between SNP and SV alleles across 53 inbred strains indicated that we have a very limited ability to infer whether SV are present using short read sequence data, even when nearby SNP alleles are known. The benefit of having a more complete map of the pattern of genetic variation was demonstrated by identifying at least three genetic factors that could underlie the unique neuroanatomic and behavioral features of BTBR mice that resemble human Autism Spectrum Disorder (ASD). Similar to the genetic findings in human ASD cohorts, the identified BTBR-unique alleles are very rare, and they cause high impact changes in genes that play a role in neurodevelopment and brain function.

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High Throughput Computational Mouse Genetic Analysis

10.1101/2020.09.01.278465 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ahmed Arslan ◽

Yuan Guan ◽

Xinyu Chen ◽

Robin Donaldson ◽

Wan Zhu ◽

...

Keyword(s):

Genetic Factors ◽

Inbred Mouse ◽

Inbred Strains ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Mitochondrial Targeting ◽

Phenotypic Data ◽

Factors Affecting ◽

Wide Range ◽

Allelic Differences

AbstractBackgroundGenetic factors affecting multiple biomedical traits in mice have been identified when GWAS data, which measured responses in panels of inbred mouse strains, was analyzed using haplotype-based computational genetic mapping (HBCGM). Although this method was previously used to analyze one dataset at a time; but now, a vast amount of mouse phenotypic data is now publicly available, which could enable many more genetic discoveries.ResultsHBCGM and a whole genome SNP map covering 43 inbred strains was used to analyze 8300 publicly available datasets of biomedical responses (1.52M individual datapoints) measured in panels of inbred mouse strains. As proof of concept, causative genetic factors affecting susceptibility for eye, metabolic and infectious diseases were identified when structured automated methods were used to analyze the output. One analysis identified a novel genetic effector mechanism; allelic differences within the mitochondrial targeting sequence affected the subcellular localization of a protein. We also found allelic differences within the mitochondrial targeting sequences of many murine and human proteins, and these could affect a wide range of biomedical phenotypes.ImplicationsThese initial results indicate that genetic factors affecting biomedical responses could be identified through analysis of very large datasets, and they provide an early indication of how this type of ‘augmented intelligence’ can facilitate genetic discovery.

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Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations

Journal of Applied Physiology ◽

10.1152/japplphysiol.01077.2006 ◽

2007 ◽

Vol 102 (6) ◽

pp. 2369-2378 ◽

Cited By ~ 125

Author(s):

Karen L. Svenson ◽

Randy Von Smith ◽

Phyllis A. Magnani ◽

Heather R. Suetin ◽

Beverly Paigen ◽

...

Keyword(s):

High Fat Diet ◽

Phenotypic Diversity ◽

Inbred Mouse ◽

Inbred Strains ◽

Mouse Strains ◽

Human Populations ◽

Large Set ◽

Inbred Mouse Strains ◽

High Fat ◽

Mineral Density

The breadth of genetic and phenotypic variation among inbred strains is often underappreciated because assessments include only a limited number of strains. Evaluation of a larger collection of inbred strains provides not only a greater understanding of this variation but collectively mimics much of the variation observed in human populations. We used a high-throughput phenotyping protocol to measure females and males of 43 inbred strains for body composition (weight, fat, lean tissue mass, and bone mineral density), plasma triglycerides, high-density lipoprotein and total cholesterol, glucose, insulin, and leptin levels while mice consumed a high-fat, high-cholesterol diet. Mice were fed a chow diet until they were 6–8 wk old and then fed the high-fat diet for an additional 18 wk. As expected, broad phenotypic diversity was observed among these strains. Significant variation between the sexes was also observed for most traits measured. Additionally, the response to the high-fat diet differed considerably among many strains. By the testing of such a large set of inbred strains for many traits, multiple phenotypes can be considered simultaneously and thereby aid in the selection of certain inbred strains as models for complex human diseases. These data are publicly available in the web-accessible Mouse Phenome Database ( http://www.jax.org/phenome ), an effort established to promote systematic characterization of biochemical and behavioral phenotypes of commonly used and genetically diverse inbred mouse strains. Data generated by this effort builds on the value of inbred mouse strains as a powerful tool for biomedical research.

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Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00483.2005 ◽

2006 ◽

Vol 291 (3) ◽

pp. L426-L435 ◽

Cited By ~ 38

Author(s):

Dao Bui Tran Anh ◽

Pedro Faisca ◽

Daniel J.-M. Desmecht

Keyword(s):

Positional Cloning ◽

Inbred Mouse ◽

Pulmonary Inflammation ◽

Differential Resistance ◽

Inbred Strains ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Crossing Experiments ◽

Syncytial Virus ◽

Uptake Data

Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection.

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A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts.

Molecular and Cellular Biology ◽

10.1128/mcb.5.8.2114 ◽

1985 ◽

Vol 5 (8) ◽

pp. 2114-2122 ◽

Cited By ~ 40

Author(s):

R E Hill ◽

P H Shaw ◽

R K Barth ◽

N D Hastie

Keyword(s):

Protease Inhibitor ◽

Multigene Family ◽

Recombinant Inbred ◽

Inbred Mouse ◽

Inbred Strains ◽

Mouse Strains ◽

Nucleotide Sequence Analysis ◽

Multigene Families ◽

Inbred Mouse Strains ◽

Ancestral Gene

The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), putative inhibitor of neutrophil elastase, and contrapsin, an inhibitor in vitro of trypsinlike proteases. We have shown by nucleotide sequence analysis that these two inhibitors are related (R. E. Hill, P. H. Shaw, P. A. Boyd, H. Baumann, and N. D. Hastie, Nature (London) 311:175-177, 1984). Here, we show that the contrapsin and alpha 1-PI genes are members of two different multigene families, each containing at least three genes in mice and rats. We established the chromosomal locations of these genes by analyzing the segregation of restriction fragment length polymorphisms in recombinant inbred mouse strains. These experiments show that the multiple genes in each family are clustered and that the two gene families are closely linked on chromosome 12. Thus the genes for contrapsin and alpha 1-PI are likely to have evolved by duplication of a common ancestral gene. The contrapsin multigene family codes for multiple mRNA transcripts in the liver. There is a genetic difference among inbred mouse strains in the regulation of two of these transcripts. In some inbred strains the transcripts are synthesized constitutively; in others they are induced by inflammation. We mapped in recombinant inbred strains the regulatory locus responsible for this genetic variation and found it is linked to the contrapsin multigene family, which suggests a cis-acting regulatory element. We also found that the contrapsin and the alpha 1-PI multigene families have acquired very different regulatory responses since the time of the gene duplication event.

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