{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:17:20Z","timestamp":1789204640065,"version":"build-2803163510"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2861,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"National Research Program on Genomic Medicine of the National Science Council of the Republic of China","award":["NSC95-3112-B-010-010"],"award-info":[{"award-number":["NSC95-3112-B-010-010"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,11]]},"abstract":"\n \n \n Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. To establish a<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n knockout mouse model, 2 lambda phage clones containing a mouse<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n genome were isolated. At 11 weeks of age, the<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 mice had hepatomegaly, hypermethioninemia, and significantly higher levels of both serum alanine aminotransferase and hepatic S-adenosylmethionine. Such phenotypes mimic patients with congenital<\/jats:bold>\n \n GNMT\n <\/jats:bold>\n 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 (<\/jats:bold>\n \n Ahcy\n <\/jats:bold>\n ), and formiminotransferase cyclodeaminase (<\/jats:bold>\n \n Ftcd\n <\/jats:bold>\n ) were significantly down-regulated in<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 mice. This report demonstrates that GNMT regulates the expression of both<\/jats:bold>\n \n Ftcd\n <\/jats:bold>\n and<\/jats:bold>\n \n Ahcy\n <\/jats:bold>\n genes. Results from pathological examinations indicated that 57.1% (8 of 14) of the<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 mice had glycogen storage disease (GSD) in their livers. Focal necrosis was observed in male<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 livers, whereas degenerative changes were found in the intermediate zones of female<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 livers. In addition, hypoglycemia, increased serum cholesterol, and significantly lower numbers of white blood cells, neutrophils, and monocytes were observed in the<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 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<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 mice: fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphate transporter.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Because<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n \u2212\/\u2212 mice phenotypes mimic those of patients with<\/jats:bold>\n \n GNMT\n <\/jats:bold>\n deficiencies and share several characteristics with GSD Ib patients, we suggest that they are useful for studies of the pathogenesis of congenital<\/jats:bold>\n \n GNMT\n <\/jats:bold>\n deficiencies and the role of GNMT in GSD and liver tumorigenesis.<\/jats:bold>\n <\/jats:p>\n 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