Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation

• DOI: 10.1073/pnas.091016398
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Shelly C. Lu; Luis Alvarez; Zong-Zhi Huang; Lixin Chen; Wei An; Fernando J. Corrales; Matías A. Avila; Gary Kanel; José M. Mato
• Keywords: Knockout mouse; Gene knockout; Metallothionein

Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A MAT2A , respectively, that catalyze the formation S -adenosylmethionine (AdoMet), principal biological methyl donor. Mature liver expresses whereas is expressed in extrahepatic tissues induced during growth dedifferentiation. To examine influence on hepatic growth, we studied effects a targeted disruption murine gene. mRNA protein levels were absent homozygous knockout mice. At 3 months, plasma level increased 776% knockouts. Hepatic AdoMet glutathione reduced by 74 40%, -adenosylhomocysteine, methylthioadenosine, global DNA methylation unchanged. The body weight 3-month-old mice was unchanged from wild-type littermates, but 40%. Affymetrix genechip system Northern Western blot analyses used to analyze differential expression genes. many acute phase-response inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, growth-related early response 1 proliferating cell nuclear animal. more susceptible choline-deficient diet-induced fatty liver. 8 developed spontaneous macrovesicular steatosis predominantly periportal mononuclear infiltration. Thus, absence resulted injury, markers an phase response, displays proliferation.