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

2007 ◽  
Vol 102 (6) ◽  
pp. 2369-2378 ◽  
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.

scholarly journals ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 386 ◽  
Author(s):  
Ayca Dogan ◽  
Peter Lasch ◽  
Christina Neuschl ◽  
Marion K Millrose ◽  
Rudi Alberts ◽  
...  
Keyword(s):  
Ftir Spectroscopy ◽  
Recombinant Inbred ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Tissue Response ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
High Fat ◽  
Recombinant Inbred Mouse

scholarly journals Divergent compensatory responses to high-fat diet between C57BL6/J and C57BLKS/J inbred mouse strains

2013 ◽  
Vol 305 (12) ◽  
pp. E1495-E1511 ◽  
Author(s):  
Emily K. Sims ◽  
Masayuki Hatanaka ◽  
David L. Morris ◽  
Sarah A. Tersey ◽  
Tatsuyoshi Kono ◽  
...  
Keyword(s):  
Weight Gain ◽  
Mouse Models ◽  
Fat Mass ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Insulin Production ◽  
High Fat ◽  
Β Cell

Impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) are polygenic disorders with complex pathophysiologies; recapitulating them with mouse models is challenging. Despite 70% genetic homology, C57BL/6J (BL6) and C57BLKS/J (BLKS) inbred mouse strains differ in response to diet- and genetic-induced obesity. We hypothesized these differences would yield insight into IGT and T2DM susceptibility and response to pharmacological therapies. To this end, male 8-wk-old BL6 and BLKS mice were fed normal chow (18% kcal from fat), high-fat diet (HFD; 42% kcal from fat), or HFD supplemented with the PPARγ agonist pioglitazone (PIO; 140 mg PIO/kg diet) for 16 wk. Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were undertaken. BL6 mice gained weight and adiposity in response to HFD, leading to peripheral insulin resistance that was met with increased β-cell proliferation and insulin production. By contrast, BLKS mice responded to HFD by restricting food intake and increasing activity. These behavioral responses limited weight gain and protected against HFD-induced glucose intolerance, which in this strain was primarily due to β-cell dysfunction. PIO treatment did not affect HFD-induced weight gain in BL6 mice, and decreased visceral fat mass, whereas in BLKS mice PIO increased total fat mass without improving visceral fat mass. Differences in these responses to HFD and effects of PIO reflect divergent human responses to a Western lifestyle and underscore the careful consideration needed when choosing mouse models of diet-induced obesity and diabetes treatment.

scholarly journals Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due to Leishmania major Infection in Four Inbred Mouse Strains

2009 ◽  
Vol 16 (11) ◽  
pp. 1529-1537 ◽  
Author(s):  
Fouad Benhnini ◽  
Mehdi Chenik ◽  
Dhafer Laouini ◽  
Hechmi Louzir ◽  
Pierre André Cazenave ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Leishmania Major ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Human Populations ◽  
Inbred Mouse Strains ◽  
Vaccine Candidates ◽  
Preclinical Evaluation ◽  
Protein Disulfide

ABSATRCT Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.

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

2010 ◽  
Vol 42A (2) ◽  
pp. 103-113 ◽  
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.

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

1973 ◽  
Vol 7 (3) ◽  
pp. 229-236 ◽  
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.

Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity

1994 ◽  
Vol 266 (5) ◽  
pp. R1423-R1428 ◽  
Author(s):  
G. P. Eberhart ◽  
D. B. West ◽  
C. N. Boozer ◽  
R. L. Atkinson
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
High Fat ◽  
Adipose Depot ◽  
Adipocyte Cell ◽  
Dietary Obesity ◽  
Lipid Stores

We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.

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

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.

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

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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