IMPT1, AN IMPRINTED GENE SIMILAR TO POLYSPECIFIC TRANSPORTER AND MULTIDRUG-RESISTANCE GENES

Human chromosome 11p15.5 and distal mouse chromosome 7 include a megab ase-scale chromosomal domain with multiple genes subject to parental i mprinting, Here we describe mouse and human versions of a novel imprin ted gene, IMPT1, which lies between IPL and p57(KIP2) and which encode s a predicted multi-membrane-spanning protein similar to bacterial and eukaryotic polyspecific metabolite transporter and multi-drug resista nce pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in t issues with metabolite transport functions, including liver, kidney, i ntestine, extra-embryonic membranes and placenta, and there is strongl y preferential expression of the maternal allele in various mouse tiss ues at fetal stages. In post-natal tissues there is persistent express ion, but the allelic bias attenuates. An allelic expression bias is al so observed in human fetal and postnatal tissues, but there is signifi cant interindividual variation and rare somatic allele switching. The fact that Impt1 is relatively repressed on the paternal allele, togeth er with data from other imprinted genes, allows a statistical conclusi on that the primary effect of human chromosome 11p15.5/mouse distal ch romosome 7 imprinting is domain-wide relative repression of genes on t he paternal homolog. Dosage regulation of the metabolite transporter g ene(s) by imprinting might regulate placental and fetal growth.