Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Deficiency of the transcription factor Cited2 in mice results in cardiac malformation, adrenal agenesis, neural tube, placental defects and partially penetrant cardiopulmonary laterality 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. 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. They suggest that appropriate modifications of maternal diet may prevent such defects in humans.

Original publication

DOI

10.1093/hmg/ddq251

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/09/2010

Volume

19

Pages

3394 - 3401

Keywords

Animals, Body Patterning, Dietary Fats, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Genotype, Homeodomain Proteins, Humans, Male, Maternal-Fetal Exchange, Mice, Mice, Inbred C57BL, Pregnancy, Repressor Proteins, Trans-Activators, Transcription Factors