Dhar M, Webb L S, Smith L, Hauser L, Johnson D, West D B
University of Tennessee Graduate School of Genome Science and Technology, Oak Ridge National Laboratory, Oak Ridge 37831-6480, USA.
Physiol Genomics. 2000 Nov 9;4(1):93-100. doi: 10.1152/physiolgenomics.2000.4.1.93.
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.
小鼠7号染色体上位于粉红眼（p）稀释位点远端的一个区域含有一个或多个基因，我们将其命名为p位点相关肥胖基因（plo1），该基因会影响身体脂肪。对于该区域最远端延伸的染色体缺失，杂合子小鼠在母系遗传该缺失时的体脂几乎是父系遗传时小鼠体脂的两倍。我们已对位于Gabrb3和Ube3a/Ipw基因之间的1兆碱基关键区域进行了物理定位，DNA测序已将P型ATP酶第三个亚家族的一个新成员定位到决定该性状的最小区域。这个我们称为p位点脂肪相关ATP酶（pfatp）的基因在人和小鼠组织中差异表达，在睾丸中表达占主导，在脂肪组织和其他器官中的表达水平较低。我们提出这个ATP酶是plo1位点上调节小鼠体脂含量的基因的主要候选者。这种表型不寻常的遗传模式表明可能存在基因组印记（已知在其他局部基因如Ube3a、Ipw中会发生），或者是孕期或哺乳期母本单倍体不足对后代体脂产生的影响。
