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Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects

Bentham, J; Michell, AC; Lockstone, H; Andrew, D; Schneider, JE; Brown, NA; Bhattacharya, S (2010) Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects. HUMAN MOLECULAR GENETICS, 19 (17). 3394 - 3401. ISSN 0964-6906 https://doi.org/10.1093/hmg/ddq251
SGUL Authors: Brown, Nigel Andrew

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Abstract

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.

Item Type: Article
Additional Information: © The Author 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited
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, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Genetics & Heredity, BIOCHEMISTRY & MOLECULAR BIOLOGY, GENETICS & HEREDITY, LEFT-RIGHT ASYMMETRY, LEFT-RIGHT AXIS, CRANIOFACIAL DEVELOPMENT, CARDIAC-MALFORMATIONS, TOOTH MORPHOGENESIS, HEART DEVELOPMENT, BODY-WEIGHT, MOUSE, OBESITY, OVERWEIGHT, 11 Medical And Health Sciences, 06 Biological Sciences
Journal or Publication Title: HUMAN MOLECULAR GENETICS
ISSN: 0964-6906
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Dates:
DateEvent
1 September 2010Published
Web of Science ID: WOS:000280704800009
URI: https://openaccess.sgul.ac.uk/id/eprint/107134
Publisher's version: https://doi.org/10.1093/hmg/ddq251

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