A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat

A region of mouse chromosome 7, just distal to the pink-eyed (p) dilution l ocus, contains a gene or genes, which we have named p-locus-associated obes ity (plo1), affecting body fat. Mice heterozygous for the most distally ext ending chromosomal deletions of this region have nearly double the body fat of mice when the deletion is inherited maternally as when it is inherited paternally. We have physically mapped the 1-Mb critical region, which lies between the Gabrb3 and Ube3a/ Ipw genes, and DNA sequencing has localized a new member of the third subfamily of P-type ATPases to the minimal region specifying the trait. This gene, which we have called p-locus fat-associate d ATPase ( pfatp) is differentially expressed in human and mouse tissues wi th predominant expression in the testis and lower levels of expression in a dipose tissue and other organs. We propose this ATPase as the prime candida te for the gene at the plo1 locus modulating body fat content in the mouse. The unusual inheritance pattern of this phenotype suggests either genomic imprinting, known to occur in other local genes (Ube3a, Ipw), or an effect of maternal haploinsufficiency during pregnancy or lactation on body fat in the progeny.