NDLI: Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero.

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Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero.

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Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Matzuk, Martin Abu-elheiga, Lutfi Finegold, Milton Mao, Jianqiang Wakil, Salih J. Chirala, Subrahmanyam S. Mahon, Kathleen Chang, Hua
Description	Author Affiliation: Chirala SS ( Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.);
Abstract	In animals, including humans, the source of long-chain saturated fatty acids is de novo synthesis, which is mediated by fatty acid synthase (FAS), ingested food, or both. To understand the importance of de novo fatty acid synthesis, we generated FAS knockout mice. The heterozygous FAS mutants (Fasn+/-) are ostensibly normal. In Fasn+/- mice the levels of FAS mRNA and the FAS activity are approximately 50% and 35% lower, respectively, than those of WT mice; hence, FAS levels are affected by gene dosage. When the Fasn+/- mutant mice were interbred, Fasn-/- mice were not produced; thus, FAS is essential during embryonic development. Furthermore, the number of Fasn+/- progeny obtained was 70% less than predicted by Mendelian inheritance, indicating partial haploid insufficiency. Even when one of the parents was WT, the estimated loss of heterozygous progeny was 60%. This loss of Fasn+/- pups appeared to be strain-specific and became more pronounced as the heterozygous females produced more litters. Most of the Fasn-/- mutant embryos died before implantation and the Fasn+/- embryos died at various stages of their development. Feeding the breeders a diet rich in saturated fatty acids did not prevent the loss of homoor heterozygotes. These observations are very important in considering teratogenic consequences of drugs aimed at inhibiting FAS activity, to reduce either obesity or the growth of cancerous tissues.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Fatty Acid Synthases Metabolism Fatty Acids Biosynthesis Heterozygote Animals DNA Primers Embryo, Mammalian Abnormalities Embryonic And Fetal Development Genetics Gene Expression Regulation, Enzymologic Mice Mice, Knockout Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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