Gene expression profiling in phosphatidylethanolamine N-methyltransferase knockout mice.
Choline is derived from the diet as well as from de novo methylation of phosphatidylethanolamine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). Pemt knockout mice have no endogenous synthesis of choline molecules. We previously reported that these mice have excess S-adenosylmethionine and hypermethylated DNA in brain, as well as increased mitosis in neural progenitor cells of the hippocampus in embryonic day 17 (E17) brain. In the present study, E17 fetal brains and adult brains were harvested and total RNA was extracted. In fetal brain, using gene expression profiling and Significance Analysis of Microarrays, we identified 107 significant genes with increased expression and 379 significant genes with decreased expression. In adult brain, we identified 381 significant genes with increased expression and 1037 significant genes with decreased expression. We observed significant changes in expression of genes regulating cell cycle (such as TP53, Fgf4, and Ing1), differentiation and neurogenesis (such as S100A4 and D14Ws), and phospholipid metabolism (such as Pip5k1a, Pitpn, and Pla2g6) as well as in a number of methyltransferase genes (including Gnmt). Some genes with expression known to be regulated by promoter methylation were suppressed in Pemt knockout brain (such as S100a4 and TP53). These findings are consistent with the biochemical changes that we previous reported in fetal brains from Pemt knockout mice. This is the first report of gene profiling in Pemt(-/-) mouse brain.
Zhu
Xiaonan
X
Department of Nutrition, CB #7461, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Zeisel
Steven H
SH
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism*; D050918:Phosphatidylethanolamine N-Methyltransferase
D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase