Differential expression of the closely linked KISS1, REN, and FLJ10761 genes in transgenic mice.
We previously reported the development and characterization of transgenic mice containing a large 160-kb P1 artificial chromosome (PAC) encompassing the renin (REN) locus from human chromosome 1. Here we demonstrate that PAC160 not only encodes REN, but also complete copies of the next upstream (KISS1) and downstream (FLJ10761) gene along human chromosome 1. Incomplete copies of the second upstream (PEPP3) and downstream (SOX13) genes are also present. The gene order PEPP3-KISS1-REN-FLJ10761-SOX13 is conserved in mice containing either one or two copies of the REN locus. Despite the close localization of KISS1, REN, and FLJ10761, they each exhibit distinct, yet overlapping tissue-specific expression profiles in humans. The tissue-specific expression patterns of REN and FLJ10761 were retained in transgenic mice containing PAC160. Expression of REN and FLJ10761 were also proportional to copy number. Expression of KISS1 in PAC160 mice showed both similarities and differences to humans. These data suggest that expression of gene blocks encoded on large genomic clones are retained when the clones are used to generate transgenic mice. Genomic elements which act to insulate genes from their neighbors are also apparently retained.
Nistala
Ravi
R
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Zhang
Xiaoji
X
Sigmund
Curt D
CD
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000235:genetics*; D023061:Gene Order / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D059648:Kisspeptins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D010053:Ovary / Q000737:chemistry / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D012083:Renin / Q000235:genetics*; D013737:Testis / Q000737:chemistry / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C106628:KISS1 protein, human; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C020125:ethanolamine kinase; D012083:Renin