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Publication : Restoration of Dlk1 and Rtl1 is necessary but insufficient to rescue lethality in intergenic differentially methylated region (IG-DMR)-deficient mice.

First Author  Takahashi N Year  2010
Journal  J Biol Chem Volume  285
Issue  34 Pages  26121-5
PubMed ID  20511218 Mgi Jnum  J:166195
Mgi Id  MGI:4839885 Doi  10.1074/jbc.M109.075325
Citation  Takahashi N, et al. (2010) Restoration of Dlk1 and Rtl1 is necessary but insufficient to rescue lethality in intergenic differentially methylated region (IG-DMR)-deficient mice. J Biol Chem 285(34):26121-5
abstractText  In the Dlk1-Dio3 imprinted domain, an intergenic differentially methylated region (IG-DMR) regulates the parental allele-specific expression of imprinted genes. The maternally inherited deletion of IG-DMR (IG-DMR((-/+))) results in perinatal lethality because of the overexpression of paternally expressed genes and repression of maternally expressed noncoding RNAs (ncRNAs), including Gtl2. To better understand the possible contribution of paternally expressed genes to the lethality, we attempted to rescue the lethality of IG-DMR((-/+)) mutants by restoring the paternally expressed genes. Because the paternally inherited Gtl2 deletion (Gtl2((+/-))) induced a decrease in the expression of paternally expressed genes, we crossed female IG-DMR heterozygous mice and male Gtl2 heterozygous mutant mice. The resultant IG-DMR((-/+))/Gtl2((+/-)) double mutant mice had normal expression levels of paternally expressed genes, and none of them showed perinatal lethality; however, most mice showed postnatal lethality with decreased expression of the maternally expressed ncRNAs. Thus, we inferred that paternally expressed genes are necessary for perinatal survivability and that maternally expressed ncRNAs are involved in postnatal lethality.
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