Effects of cerebral ischemia in mice lacking DNA methyltransferase 1 in post-mitotic neurons.
DNA methylation is important for controlling gene expression and is catalyzed by DNA methyltransferase (Dnmt1) an enzyme abundant in brain. We recently demonstrated that mice expressing reduced levels of Dnmt1 are protected from cerebral ischemia. Here, we used the cre/loxP system to produce conditional mutants that lack Dnmt 1 in postmitotic neurons of the postnatal brain. We demonstrate that animals heterozygous for the conditional allele (Dnmt11lox/+) have significantly smaller infarcts following 1 h middle cerebral artery occlusion/reperfusion compared to their wildtype litters. Surprisingly, mice with a deletion of Dnmt1 in post-mitotic neurons (Dnmt11lox/c) were not protected. In conclusion, we demonstrate that reduced levels of Dnmt1, but not its absence, in post-mitotic neurons protect from ischemic brain injury.
Endres
M
M
Experimental Neurology, Department of Neurology, Charité Hospital, Humboldt-University, Schumannstr 20/21, D-10098 Berlin, Germany.
Fan
G
G
Meisel
A
A
Dirnagl
U
U
Jaenisch
R
R
D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001831:Body Temperature / Q000235:genetics; D001921:Brain / Q000201:enzymology* / Q000254:growth & development / Q000503:physiopathology; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D002544:Cerebral Infarction / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency* / Q000235:genetics; D019175:DNA Methylation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse