國家衛生研究院 NHRI:Item 3990099045/2238
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    题名: Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver
    作者: Liu, SP;Li, YS;Chen, YJ;Chiang, EP;Li, AFY;Lee, YH;Tsai, TF;Hsiao, M;Hwang, SF;Chen, YMA
    贡献者: Division of Molecular and Genomic Medicine
    摘要: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. To establish a Gnmt knockout mouse model, 2 lambda phage clones containing a mouse Gnmt genome were isolated. At I I weeks of age, the Gnmt(-/-) mice had hepatomegaly, hypermethioninemia, and significantly higher levels of both serum alanine aminotransferase and hepatic S-adenosylmethionine. Such phenotypes mimic patients with congenital GNMT deficiencies. A real-time polymerase chain reaction analysis of 10 genes in the one-carbon metabolism pathway revealed that 5,10-methylenetetrahydrofolate reductase, S-adenosylhomocysteine hydrolase (Ahcy), and formiminotransferase cyclodeaminase (Ftcd) were significantly down-regulated in Gnmt(-/-) mice. This report demonstrates that GNMT regulates the expression of both Ftcd and Ahcy genes. Results from pathological examinations indicated that 57.1% (8 of 14) of the Gnmt(-/-) mice had glycogen storage disease (GSD) in their livers. Focal necrosis was observed in male Gnmt(-/-) livers, whereas degenerative changes were found in the intermediate zones of female Gnmt(-/-) livers. In addition, hypoglycemia, increased serum cholesterol, and significantly lower numbers of white blood cells, neutrophils, and monocytes were observed in the Gnmt(-/-) mice. A real-time polymerase chain reaction analysis of genes involved in the gluconeogenesis pathways revealed that the following genes were significantly down-regulated in Gnmt(-/-) mice: fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphate transporter. Conclusion: Because Gnmt(-/-) mice phenotypes mimic those of patients with GNMT deficiencies and share several characteristics with GSD Ib patients, we suggest that they are useful for studies of the pathogenesis of congenital GNMT deficiencies and the role of GNMT in GSD and liver tumorigenesis.
    关键词: Gastroenterology & Hepatology
    日期: 2007-11
    關聯: Hepatology. 2007 Nov;46(5):1413-1425.
    Link to: http://dx.doi.org/10.1002/hep.21863
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-9139&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000250701200015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=36349011287
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