Synergistic gene interactions control the induction of the mitochondrial uncoupling protein (Ucp1) gene in white fat tissue

Among a selected group of mouse strains susceptible to dietary obesity, tho se with an enhanced capacity for Ucp1 and brown adipocyte induction in whit e fat preferentially lost body weight following adrenergic stimulation. Eas ed on the generality of this mechanism for reducing obesity, a genetic anal ysis was initiated to identify genes that control brown adipocyte induction in white fat depots in mice, Quantitative trait locus (QTL) analysis was p erformed using the variations of retroperitoneal fat Ucp1 mRNA expression i n progeny of genetic crosses between the A/J and C57BL/6J parental strains and selected AXE recombinant inbred strains. Three A/J-derived loci on chro mosomes 2, 3, and 8 and one C57BL/6J locus on chromosome 19 were linked to Ucp1 induction in retroperitoneal fat. Although A/J-derived alleles seemed to contribute to elevated Ucp1 expression, the C57BL/6J allele on chromosom e 19 increased Ucp1 mRNA to levels higher than parental values. Thus, novel patterns of C57BL/6J and A/J recombinant genotypes among the four mapped l oci resulted in a transgressive variation of Ucp1 phenotypes, Although the extent, of the interchromosomal interactions have not been fully explored, strong synergistic interactions occur between a C57BL/6J allele on chromoso me 19 and an A/J allele on chromosome a In addition to selective synergisti c interactions between loci, variations in recessive and dominant effects a lso contribute to the final levels of Ucp1 expression.