Mechanism sharing between genetic and gestational hypoxia-induced cardiac anomalies

Purpose: Mutations in several genetic loci lead to cardiac anomalies, with mutations in transcription factor NKX2-5 gene being one of the largest mutations known. Gestational hypoxia, such as seen in high-altitude pregnancy, has been known to affect cardiac development, and this paper aims to uncover information about the underlying mechanisms of this phenomena. Methods: Wild-type female mice were mated with Nkx2-5 mutant males, to produce offsprings. The pregnant females were then separated into two groups, one left in normal air and one breathing hypoxic, 14% oxygen, air from gestation day 10.5 to 12.5. Hearts were dissected from E12.5 embryos, subjected to RNA purification followed by RNA-seq. Wild-hypoxia and mutant-normoxia were compared to control wild-normoxia. Conclusions: The results of our study provide insights into a common molecular mechanism underlying non-genetic/epigenetic and genetic cardiac anomalies. Overall design: Embryonic mice were produced with either wild-type or mutant genomes, and some from each group were exposed to hypoxia during gestation, then physical analysis and RNA sequencing was done on the embryos.

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Moumne O, Chowdhurry R, Doll C, Pereira N, Hashimi M, Grindrod T, Dollar JJ, Riva A, Kasahara H