Restoration of Dlk1 and Rtl1 is necessary but insufficient to rescue lethality in intergenic differentially methylated region (IG-DMR)-deficient mice.
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.
Takahashi
Nozomi
N
Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-0054, Japan.
Kobayashi
Ryota
R
Kono
Tomohiro
T
D000818:Animals; D002135:Calcium-Binding Proteins; D019175:DNA Methylation; D021901:DNA, Intergenic; D005260:Female; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011257:Pregnancy Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D013534:Survival
D002135:Calcium-Binding Proteins; D021901:DNA, Intergenic; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C422882:MEG3 non-coding RNA, mouse; D011257:Pregnancy Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; C526773:Rtl1 protein, mouse