IMPT1, an imprinted gene similar to polyspecific transporter and multi-drug resistance genes.
Human chromosome 11p15.5 and distal mouse chromosome 7 include a megabase-scale chromosomal domain with multiple genes subject to parental imprinting. Here we describe mouse and human versions of a novel imprinted gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a predicted multi-membrane-spanning protein similar to bacterial and eukaryotic polyspecific metabolite transporter and multi-drug resistance pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues with metabolite transport functions, including liver, kidney, intestine, extra-embryonic membranes and placenta, and there is strongly preferential expression of the maternal allele in various mouse tissues at fetal stages. In post-natal tissues there is persistent expression, but the allelic bias attenuates. An allelic expression bias is also observed in human fetal and post-natal tissues, but there is significant interindividual variation and rare somatic allele switching. The fact that Impt1 is relatively repressed on the paternal allele, together with data from other imprinted genes, allows a statistical conclusion that the primary effect of human chromosome 11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative repression of genes on the paternal homolog. Dosage regulation of the metabolite transporter gene(s) by imprinting might regulate placental and fetal growth.
Dao
D
D
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Frank
D
D
Qian
N
N
O'Keefe
D
D
Vosatka
R J
RJ
Walsh
C P
CP
Tycko
B
B
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002648:Child; D002880:Chromosomes, Human, Pair 11; D019450:Genes, MDR / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D010920:Placenta / Q000378:metabolism; D011110:Polymorphism, Genetic; D014018:Tissue Distribution
D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; C111653:SLC22A18 protein, human