BioProject

Deficiency of the transcription factor Cited2 in mice results in cardiac malformation, adrenal agenesis, neural tube, placental defects, and partially penetrant left-right patterning defects resulting from an abnormal Nodal->Pitx2c pathway. More...

Deficiency of the transcription factor Cited2 in mice results in cardiac malformation, adrenal agenesis, neural tube, placental defects, and partially penetrant left-right patterning defects resulting from an abnormal Nodal->Pitx2c pathway. Here we show that a maternal high-fat diet more than doubles the penetrance of laterality defects and, surprisingly, induces palatal clefting in Cited2 deficient embryos. Both maternal diet and Cited2 deletion reduce embryo weight and kidney and thymus volume. Expression profiling identified 40 embryonic transcripts including Pitx2 that were significantly affected by embryonic genotype-maternal diet interaction. We show that a high-fat diet reduces Pitx2c levels >2 fold in Cited2 deficient embryos and that Pitx2c deficiency results in cleft palate. Taken together, these results define a novel interaction between maternal high-fat diet and embryonic Cited2 deficiency that affects Pitx2c expression and results in abnormal laterality and cleft palate. Overall design: Two-factor design: diet (high fat or control) and genotype (Cited2 knockout or wildtype) with n=3 for each of the 4 factor combinations Less...