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A locus on mouse Chromosome 9 (Adip5) affects the relative weight of the gonadal but not retroperitoneal adipose depot

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Abstract

To identify the gene or genes on mouse Chromosome 9 that contribute to strain differences in fatness, we conducted an expanded mapping analysis to better define the region where suggestive linkage was found, using the F2 generation of an intercross between the C57BL/6ByJ and 129P3/J mouse strains. Six traits were studied: the summed weight of two adipose depots, the weight of each depot, analyzed individually (the gonadal and retroperitoneal depot), and the weight of each depot (summed and individual) relative to body size. We found significant linkage (LOD = 4.6) that accounted for the relative weight of the summed adipose depots, and another for the relative weight of the gonadal (LOD = 5.3) but not retroperitoneal (LOD = 0.9) adipose depot. This linkage is near marker rs30280752 (61.1 Mb, Build 34) and probably is equivalent to the quantitative trait locus (QTL) Adip5. Because the causal gene is unknown, we identified and evaluated several candidates within the confidence interval with functional significance to the body fatness phenotype (Il18, Acat1, Cyp19a1, Crabp1, Man2c1, Neil1, Mpi1, Csk, Lsm16, Adpgk, Bbs4, Hexa, Thsd4, Dpp8, Anxa2, and Lipc). We conclude that the Adip5 locus is specific to the gonadal adipose depot and that a gene or genes near the linkage peak may account for this QTL.

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Acknowledgments

Grants from the National Institutes of Health funded this research (R01DK058797 to DRR, R01AA011028 and R01DC00882 to AAB, and R01DK046791 and R01AA12715 to MGT). The authors acknowledge Matthew Thomas, Senior Scientist at DNAPrint, for his assistance with genotyping services, and Dr. Kelly Ewen-White and Paige Stevenson, the Genotyping Section at the Australian Genome Research Facility, for additional genotyping. Maria Theodorides and Fujiko Duke provided excellent technical assistance. Early data collection for this experiment was conducted in the laboratory of R. Arlen Price, and his support is gratefully acknowledged. Patricia Watson provided helpful editorial advice. Discussions with Hong Ji, Mark I. Friedman, and Caroline M. Pond enhanced the quality of this work.

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Correspondence to Danielle R. Reed.

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The following sequences have been submitted to the GenBank database: Thsd4: Accession Nos. DQ424862 and DQ517441 and Lsm16: Accession Nos. DQ240818-DQ240819.

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McDaniel, A.H., Li, X., Tordoff, M.G. et al. A locus on mouse Chromosome 9 (Adip5) affects the relative weight of the gonadal but not retroperitoneal adipose depot. Mamm Genome 17, 1078–1092 (2006). https://doi.org/10.1007/s00335-006-0055-1

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