Identification of a congenic mouse line with obesity and body length phenotypes
2004
Warden, Craig H. | Stone, Steven | Chiu, Sally | Diament, Adam L. | Corva, Pablo | Shattuck, Donna | Riley, Robyn | Hunt, Steven C. | Easlick, Juliet | Fisler, Janis S. | Medrano, Juan F.
Our primary objective was to discover simplified mouse models corresponding to human obesity linkages. We used the B10.UW– H3ᵇwe Pax1ᵘⁿaᵗ/Sn (B10.UW) congenic strain, a subcongenic strain with a reduced UW strain donor region, and their C57BL/10SnJ background strain. The congenic and subcongenic UW strain donor regions are on mouse Chr 2. We measured body length [anal-nasal (AN) length], summed fat depot weights normalized for body weight (Adiposity Index, AI), and percentage of body weight that is lipid. The B10.UW congenic and subcongenic strains have significantly smaller AN lengths (p < 0.0001) and have a significantly lower AI and percentage of body weight as fat than the background strain (p < 0.0001). In an F₂ intercross of the congenic and background strains, AN and AI were both linked to the distal half of the donor region with LOD scores greater than 19 and 5, respectively. F₂ haplotypes identified a minimal region for AN linkage of 0.8 megabases (Mb) that is estimated to express four genes in the current Celera mouse genome assembly. We narrowed the most likely location of the obesity gene to 15 Mb whose homologous genes are all located on human Chr 20 in the region surrounding the centromere. Since a previous study identified human obesity linkage peaking near the centromere, then the B10.UW mice may exhibit obesity due to the homologous gene.
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