Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A

SPECIFIC AIMSIn mammals, two genes, MAT1A and MAT2A, encode for methionine adenosyltransferase (MAT), which catalyzes formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor and precursor for polyamines. We have shown that MAT1A knockout (referred to as MATO) mice have markedly lower hepatic AdoMet levels, hepatic hyperplasia, and develop spontaneous steatohepatitis. The aim of the current study was to examine the mechanisms and consequences of some of these changes.PRINCIPAL FINDINGS1. Chronic hepatic AdoMet deficiency led to an aberrant gene expression profile reminiscent of diabetes, obesity, and other conditions associated with steatohepatitisAbsence of hepatic MAT1A resulted in chronic hepatic AdoMet deficiency. To examine the consequence of this on differential hepatic gene expression profiles, we analyzed results obtained using oligonucleotide microarrays from 3-month-old wild-type (WT) and MATO mice according to the biological processes in which they participate. Most gen...