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Congenic mice demonstrate the presence of QTLs conferring obesity and hypercholesterolemia on chromosome 1 in the TALLYHO mouse

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Abstract

The TALLYHO (TH) mouse presents a metabolic syndrome of obesity, type 2 diabetes, and hyperlipidemia. Highly significant quantitative trait loci (QTLs) linked to adiposity and hypercholesterolemia were previously identified on chromosome (Chr) 1 in a genome-wide scan of F2 mice from C57BL/6J (B6) x TH. In this study, we generated congenic mouse strains that carry the Chr 1 QTLs derived from TH on a B6 background; B6.TH-Chr1-128Mb (128Mb in size) and B6.TH-Chr1-92Mb (92Mb in size, proximally overlapping). We characterized these congenic mice on chow and high fat (HF) diets. On chow, B6.TH-Chr1-128Mb congenic mice exhibited a slightly larger body fat mass compared with B6.TH-Chr1-92Mb congenic and B6 mice, while body fat mass between B6.TH-Chr1-92Mb congenic and B6 mice was comparable. Plasma total cholesterol levels were significantly higher in B6.TH-Chr1-128Mb congenics compared to B6.TH-Chr1-92Mb congenic and B6 mice. Again, there was no difference in plasma total cholesterol levels between B6.TH-Chr1-92Mb congenic and B6 mice. All animals gained more body fat and exhibited higher plasma total cholesterol levels when fed HF diets than fed chow, but these increases were greater in B6.TH-Chr1-128Mb congenics than in B6.TH-Chr1-92Mb congenic and B6 mice. These results confirmed the effect of the 128Mb TH segment from Chr 1 on body fat and plasma cholesterol values and showed that the distal segment of Chr 1 from TH is necessary to cause both phenotypes. Through bioinformatic approaches, we generated a list of potential candidate genes within the distal region of Chr 1 and tested Ifi202b and Apoa2. We conclude that Chr 1 QTLs largely confer obesity and hypercholesterolemia in TH mice and can be promising targets for identifying susceptibility genes. Congenic mouse strains will be a valuable resource for gene identification.

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Acknowledgements

This work was supported in part by NIH/NIDDK Grant R01DK077202, American Heart Association Grant 0855300E, NIH/NIGMS P20GM103434 which funds the IDeA WV-INBRE program and supports the WV-INBRE Bioinformatics Core Facility, and institutional start-up funding from Marshall University to JHK.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA

    Jacaline K. Parkman, James Denvir, Xia Mao, Kristy D. Dillon, Sofia Romero & Jung Han Kim

  2. Department of Animal Science, University of Tennessee, Knoxville, TN, 37996, USA

    Arnold M. Saxton

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  1. Jacaline K. Parkman
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  2. James Denvir
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  3. Xia Mao
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  4. Kristy D. Dillon
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  6. Arnold M. Saxton
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  7. Jung Han Kim
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Correspondence to Jung Han Kim.

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Parkman, J.K., Denvir, J., Mao, X. et al. Congenic mice demonstrate the presence of QTLs conferring obesity and hypercholesterolemia on chromosome 1 in the TALLYHO mouse. Mamm Genome 28, 487–497 (2017). https://doi.org/10.1007/s00335-017-9719-2

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