Linking cellular zinc status to body weight and fat mass: mapping quantitative trait loci in Znt7 knockout mice

Zinc transporter 7 (Znt7, Slc30a7) knockout (KO) mice display abnormalities in body weight gain and body adiposity. Regulation of body weight and body fat accumulation is complex, involving multiple genetic and environmental factors. To understand how zinc homeostasis influences body weight and fat deposit and to identify quantitative trait loci (QTLs) that link zinc metabolism to growth and adiposity, we conducted a genome-wide mapping study using male F2 Znt7 KO mice and wild-type (WT) littermates with a mixed 129P1/ReJ and C57BL/6J genetic background. The mice were fed a semi-purified diet containing 30-mg Zn/kg diet at weaning. Body weights and fat pad weights including epididymal, retroperitoneal, and femoral subcutaneous fat pads were measured at 16 weeks of age. We detected two significant QTLs (p < 0.05) for body weight and fat deposit. One was in the F2 Znt7 KO population and the other in the F2 WT population. In Znt7 KO mice, the body weight and fat deposit was significantly linked to a locus on chromosome 7 ranging from 64.3 to 78.3 Mb. In WT mice, a significant linkage of retroperitoneal fat mass was found on chromosome 8 between 14.5 and 63.5 Mb. In addition, several other suggestive QTLs (p < 0.63) for body weight and fat accumulation were detected in Znt7 KO and WT mice. In conclusion, the QTLs identified in this study may provide new hints to uncover the genes linking cellular zinc status to growth and body fat accumulation.