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Physiol. Genomics 4: 93-100, 2000;
1094-8341/00 $5.00
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Received 22 June 2000; accepted in final form 15 September 2000.
Physiological Genomics 4:93-100 (2000)
1094-8341/00 $5.00 © 2000 American Physiological Society

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

MADHU DHAR1, LISA S. WEBB1, LAUREL SMITH2, LOREN HAUSER1, DABNEY JOHNSON1,2 and DAVID B. WEST3,4

1 University of Tennessee Graduate School of Genome Science and Technology, Oak Ridge National Laboratory, Oak Ridge 37831-6480
2 Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831
3 Department of Molecular Medicine, Lawrence Berkeley National Laboratory, Donner Laboratory, Berkeley 94720
4 Pfizer Global Research and Development, Alameda, California 94502

A region of mouse chromosome 7, just distal to the pink-eyed (p) dilution locus, contains a gene or genes, which we have named p-locus-associated obesity (plo1), affecting body fat. Mice heterozygous for the most distally extending 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-associated ATPase (pfatp) is differentially expressed in human and mouse tissues with predominant expression in the testis and lower levels of expression in adipose tissue and other organs. We propose this ATPase as the prime candidate 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.

mouse chromosome 7; quantitative trait loci; adiposity




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