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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation
Authors: Lu, S.Z. (S. Z.)
Álvarez, L. (Lluis)
Huang, Z.Z. (Zong-Zhi)
Chen, L. (L)
An, W.G. (Won G.)
Corrales, F.J. (Fernando José)
Avila, M.A. (Matías Antonio)
Kanel, G. (G.)
Mato, J.M. (José María)
Keywords: Cell Division/genetics
Gene Expression Regulation, Enzymologic
Genetic Predisposition to Disease
Liver Cirrhosis, Experimental/genetics
Methionine Adenosyltransferase/physiology
Issue Date: 2001
Publisher: National Academy of Sciences
Publisher version: http://www.pnas.org/content/98/10/5560
ISSN: 1091-6490
Citation: Lu SC, Alvarez L, Huang ZZ, Chen L, An W, Corrales FJ, et al. Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci U S A 2001 May 8;98(10):5560-5565.
Abstract
Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is induced during liver growth and dedifferentiation. To examine the influence of MAT1A on hepatic growth, we studied the effects of a targeted disruption of the murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous knockout mice. At 3 months, plasma methionine level increased 776% in knockouts. Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged. The body weight of 3-month-old knockout mice was unchanged from wild-type littermates, but the liver weight was increased 40%. The Affymetrix genechip system and Northern and Western blot analyses were used to analyze differential expression of genes. The expression of many acute phase-response and inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, and growth-related genes, including early growth response 1 and proliferating cell nuclear antigen, is increased in the knockout animal. At 3 months, knockout mice are more susceptible to choline-deficient diet-induced fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular steatosis and predominantly periportal mononuclear cell infiltration. Thus, absence of MAT1A resulted in a liver that is more susceptible to injury, expresses markers of an acute phase response, and displays increased proliferation.
Permanent link: http://hdl.handle.net/10171/21475
Appears in Collections:DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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