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大鼠中的基因组印记:Igf2和H19基因的连锁以及胚胎发育过程中亲代等位基因的特异性表达相反。

Genomic imprinting in the rat: linkage of Igf2 and H19 genes and opposite parental allele-specific expression during embryogenesis.

作者信息

Overall M, Bakker M, Spencer J, Parker N, Smith P, Dziadek M

机构信息

Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, 3052, Australia.

出版信息

Genomics. 1997 Oct 15;45(2):416-20. doi: 10.1006/geno.1997.4933.

Abstract

Igf2 and H19 are closely linked imprinted genes in both mice and humans that are expressed from opposite parental alleles. In this study we demonstrate that these two genes are also closely linked in the rat, with the H19 gene mapping to within 145 kb of Igf2 on rat chromosome 1. We identified polymorphisms in H19 and Igf2 transcripts in two inbred rat strains and determined the expression of the parental alleles in F1 offspring. The H19 gene was shown to be expressed exclusively from the maternal allele in all fetal and neonatal tissues. Monoallelic expression of Igf2 from the paternal allele was found in all tissues except the leptomeninges and choroid plexus. Igf2 in the choroid plexus was monoallelic at days 13.5 and 15.5 of gestation with a switch to biallelic expression by day 18.5, demonstrating a loss of imprinting after the choroid plexus has differentiated. Biallelic expression of Igf2 was observed in the leptomeninges at all fetal and neonatal stages analyzed. These studies demonstrate conservation of imprinting of two closely linked genes transcribed from opposite parental alleles in a species other than human or mouse. A comparative approach between different species will be important in defining the mechanisms that regulate the tissue-specific expression of imprinted genes.

摘要

Igf2和H19是小鼠和人类中紧密连锁的印记基因,它们从相反的亲本等位基因表达。在本研究中,我们证明这两个基因在大鼠中也紧密连锁,H19基因定位于大鼠1号染色体上Igf2基因145 kb范围内。我们在两个近交大鼠品系中鉴定了H19和Igf2转录本中的多态性,并确定了F1代后代中亲本等位基因的表达情况。结果显示,H19基因在所有胎儿和新生儿组织中仅从母本等位基因表达。除软脑膜和脉络丛外,Igf2在所有组织中均从父本等位基因单等位基因表达。脉络丛中的Igf2在妊娠第13.5天和15.5天是单等位基因表达,到第18.5天转变为双等位基因表达,表明脉络丛分化后印记丢失。在所有分析的胎儿和新生儿阶段,软脑膜中均观察到Igf2的双等位基因表达。这些研究证明了在人类或小鼠以外的物种中,从相反亲本等位基因转录的两个紧密连锁基因的印记保守性。在不同物种之间采用比较方法对于确定调控印记基因组织特异性表达的机制很重要。

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