Experiment
Selective genotyping (using 80 microsatellite markers at an average spacing of 20 cM) was performed population of (C57BL/6J x A/J)F1 x A/J backcross animals to identify loci associated with induction of uncoupling protein 1 (Ucp1) in white fat tissue. The animals were exposed to cold for 1 week to induce Ucp1. Enhanced induction of Ucp1 is correlated to the ability to lose weight in obesity-prone inbred mouse strains. Inbred strain C57BL/6J exhibits lower Ucp1 induction compared to A/J. Four loci, Iba1 (induction of brown adipocytes), Iba2, Iba3, and Iba4 were identified on mouse Chromosome 2 at 47 cM, mouse Chromosome 3 at 49.7 cM, mouse Chromosome 8 at 31 cM, and mouse Chromosome 19 at 20 cM, respectively. Iba1 yields a peak LOD = 8.59 at D2Mit66 with a QTL range from 40.4 cM - 50.3 cM, Iba2 yields a peak LOD = 4.98 at D3Mit10 with a QTL range from 41 cM - 58.8 cM, and Iba3 yields a peak LOD = 12.54 at D8Mit128 with a QTL range from 30 cM - 33 cM. A/J-derived alleles are associated with enhanced Ucp1 induction at Iba1, Iba2, and Iba3. Possible candidate genes in the region of Iba1 include Gad1, Chrna1 (Acra), and HoxD. Possible candidate genes in the region of Iba2 include Gja5, Nras, Tshb, Kcna2, Gja8, Kcna3, Kcna4, and Kcna8. Possible candidate genesin the region of Iba3 include Jak3, Npy1r, and Pde4c. Iba4 yields a peak LOD = 3.63 at D19Mit86 with a QTL range from 22 cM - 24 cM. C57BL/6J alleles are associated with enhanced Ucp1 induction at Iba4. Possible candidate genes in the region of Iba4 are Vldlr, Rln, and Jak2. There evidence of interaction between Iba3 and Iba4. Animals carrying the A/J allele at Iba3 and the C57BL/6J allele at Iba4 exhibit the highest levels of Ucp1 induction.
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