Abstract
BACKGROUND: Congenic mouse strains contain donor mouse strain DNA in genomes otherwise identical to a background strain. They can be used to identify defined chromosomal regions containing obesity genes with small effects.
OBJECTIVE: The objective of this study was to discover congenic strains containing genes that influence body fat in mice and to examine interactions between these genes.
DESIGN: A survey of congenic strains showed that the B6.C-Tyrc H1b Hbbd/By (B6.C-H1) congenic strain, with a 24 centiMorgan (cM) donor region from strain BALB/cBy on chromosome 7, had 50% less fat than background C57BL/6By (B6By) mice. The congenic donor region was then divided into 11 smaller overlapping subcongenic regions. Genotype effects on obesity traits in the subcongenics were determined by breeding heterozygotes for each line and comparing phenotypes of littermates with different donor genotypes.
RESULTS: At least three subcongenic strains, two with overlapping donor regions and one with a nonoverlapping donor strain region, were found to exhibit significant influences of donor region genotype on obesity. A cross of the two overlapping subcongenics demonstrated that a single gene in the overlap region could not account for the observed obesity effects. We also observed significant obesity differences between genetically identical progeny that were contingent on the genotype of their subcongenic mothers.
CONCLUSIONS: These results demonstrate the existence of at least three genes influencing obesity in three subcongenic strains with donor strain chromosomal regions whose size ranges from 0.5 to 5 cM. A maternal effect gene influencing obesity may be present in some subcongenic strains.
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Acknowledgements
We thank Sue Bennett, Noreene Shibata, Sally Chiu and Daniel Petroni for their help in mouse colony management and phenotyping. This research was supported by NIH NIDDK RO1 DK52581 and PHS DK07355. Both Adam Diament and Craig Warden contributed to study design, data analysis and writing. Adam Diament was solely responsible for data collection. Neither author has any financial or personal interest in any company or organization sponsoring the research.
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Supported by NIH DK52581, DK07355 and the UC Davis Clinical Nutrition Research Unit, DK35747.
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Diament, A., Warden, C. Multiple linked mouse chromosome 7 loci influence body fat mass. Int J Obes 28, 199–210 (2004). https://doi.org/10.1038/sj.ijo.0802516
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DOI: https://doi.org/10.1038/sj.ijo.0802516
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