Deletion of the H19 transcription unit reveals the existence of a putative imprinting control element.
The distal region of mouse chromosome 7 contains a cluster of imprinted genes that includes H19 and Igf2 (insulin-like growth factor 2). H19 is expressed as an untranslated RNA found at high levels in endodermal and mesodermal embryonic tissues. This gene is imprinted and exclusively expressed from the allele of maternal origin. The Igf2 gene shows a similar pattern of expression but is expressed from the paternal allele. We have generated a targeted deletion of the H19 transcription unit by insertion of a neo replacement cassette. The homozygous mutant animals are viable and fertile and display an overgrowth phenotype of 8% compared with wild-type littermates. This is associated with the disruption of Igf2 imprinting and the consequent biallelic expression of this gene. A striking feature of the recombinant H19 allele is the occurrence of a parental imprint set on the neo replacement cassette. Therefore imprinting of the H19 locus is independent of the H19 gene itself. Taken together with the results of a larger H19 mutation described previously, this indicates that an imprinting control element is located within the region 10 kb upstream of H19.
Ripoche
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Institut Cochin de Génétique Moleculaire (ICGM), Institut National dela Santé et de la Recherche Médicale (INSERM) U257, Paris, France.
Kress
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Poirier
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Dandolo
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D000818:Animals; D000831:Animals, Newborn; D002678:Chimera; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D019175:DNA Methylation; D005260:Female; D018390:Gene Targeting; D018392:Genomic Imprinting; D015698:Genomic Library; D006579:Heterozygote; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D005810:Multigene Family; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014158:Transcription, Genetic
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II