Abstracts (poster) - Wissenschaft Online

Sandra Weiss, Ralf Gilsbach, Frederico Barreto, Achim Lother, Lutz Hein
Heart failure and fibrosis induced by overexpression of methyl-
CpG- binding protein 2 (MeCP2) in transgenic mice
Regulation of gene expression by histone acetylation/deacetylation plays a basic role in
the development and progression of cardiac hypertrophy and failure. Genes can be
silenced by histone deacetylation and binding of methyl-CpG-binding proteins to
methylated promoter areas. In the present study, we analyzed expression of MeCP2 in
the heart during the development of heart failure and investigated its cardiac function in
a transgenic mouse model.
Expression of MeCP2 was determined in wild-type (WT) and α 2ABC -adrenoceptordeficient
(α 2ABC KO) mice after induction of cardiac hypertrophy by transverse aortic
constriction (TAC). In WT mice, TAC increased ventricle/body weight ratio by 154±12%
after 8 weeks. In WT TAC mice, cardiac MeCP2 mRNA levels were decreased by 92±5%
as compared to the sham group. Chronic elevation of circulating catecholamines in
α 2ABC KO mice caused a similar decrease in cardiac MeCP2 mRNA levels to 27±15 % of
WT controls. To test if MeCP2 expression affects cardiac myocyte growth, rat neonatal
cardiac myocytes were cotransfected with GFP and MeCP2 or empty vector. Cardiac
myocyte areas increased from 467±26 µm 2 at baseline to 637±44 µm 2 after
phenylephrine treatment and to 755±40 µm 2 after phenylephrine plus MeCP2
transfection. Beyond transgenic mice expressing MeCP2 under control of the α-MHC gene
promoter were generated. Unexpectedly, all MeCP2 transgenic founder mice were lost at
6-8 weeks of age due to a severe cardiomyopathy.
These results reveal that expression of MeCP2 is regulated during heart failure and
cardiac-specific expression in transgenic mice induces severe postnatal cardiomyopathy.
Thus, MeCP2 may play an important role in the control of gene expression during the
development of heart failure.
contact:
Sandra Weiss
Universität Freiburg
Inst. für Experimentelle und Klinische Pharmakologie
sandra.weiss@pharmakol.uni-freiburg.de
Albertstr. 25
79104 Freiburg (Germany)