期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 364, 期 3, 页码 556-560出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.10.026
关键词
NAT/arylamine N-acetyltransferase; folate; NTD; gender; sex ratio; breast cancer
资金
- Biotechnology and Biological Sciences Research Council [BB/C511356/1, BB/C515771/1] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/C511356/1, BB/C515771/1, BBC5113561] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
The mouse arylamine N-acetyltransferase 2 (Nat2) and its homologue (NAT1) in humans are known to detoxify xenobiotic arylamines and are also thought to play a role in endogenous metabolism. Human NAT1 is highly over-expressed in estrogen receptor positive breast tumours and is implicated in susceptibility to neural tube defects. In vitro assays have suggested an endogenous role for human NAT1 in folate metabolism, but in vivo evidence to support this hypothesis has been lacking. Mouse Nat2 provides a good model to study human NAT1 as it shows similar expression profiles and substrate specificities. We have generated transgenic mice lacking a functional Nat2 gene and compared the urinary levels of acetylated folate metabolite para-aminobenzoylglutamate in Nat2 knockout and Nat2 wild-type mice. These results support an in vivo role for mouse Nat2/human NAT1 in folate metabolism. In addition, effects of the Nat2 deletion on sex ratios and neural tube development are described. (C) 2007 Elsevier Inc. All rights reserved.
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