Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains

The inheritance of adiposity levels has been investigated in an intercross of the obese, diabetes-prone NZO and the small, lean SM mouse strains. Adip osity index (AI) was defined as the sum of four fat pad weights divided by body weight. DNA pools from fat and lean mice were analyzed with microsatel lite variants to screen the genome for quantitative trait loci (QTLs) affec ting AI. Ten significant QTLs affecting AI were identified on Chromosome (C hr) 1 (three loci), Chr 2, Chr 5 (two loci), Chr 6 (two loci), Chr 7, and C hr 17. Most of the QTLs appear to be novel. Several QTLs differentially aff ect specific fat depots. Thus, Chr 2 and Chr 7 QTLs affect gonadal more tha n inguinal fat, while the converse is true for the Chr 17 QTL. Gender influ ences the expression of several of the: QTLs. For example, effects of the p roximal Chr 1 QTL (Obq7) on AI appears to be primarily in males. The proxim al AI QTL on Chr 6 (Obq13) maps near the neuropeptide Y (Npy) locus. Sequen ce analysis of the Npy gene revealed a I-nucleotide deletion within a highl y conserved portion of the 3' untranslated region in strain NZO. However, t he deletion is polymorphic among mouse strains. Furthermore, lack of associ ation between this same variant and AI in previously analyzed crosses raise s doubt that it is the basis of Obq13. The present cross is the fourth in a series of intercrosses among 10 inbred strains arranged such that each str ain is crossed with each adjacent strain within a circle. This design affor ds multiple opportunities to analyze each segregating QTL.