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Nkx2.5 homeoprotein regulates expression of gap junction protein connexin 43 and sarcomere organization in postnatal cardiomyocytes

Authors :
Kasahara, Hideko
Ueyama, Tomomi
Wakimoto, Hiroko
Liu, Margaret K.
Maguire, Colin T.
Converso, Kimber L.
Kang, Peter M.
Manning, Warren J.
Lawitts, Joel
Paul, David L.
Berul, Charles I.
Izumo, Seigo
Source :
Journal of Molecular & Cellular Cardiology. Mar2003, Vol. 35 Issue 3, p243. 14p.
Publication Year :
2003

Abstract

Nkx2.5, an evolutionarily conserved homeodomain containing transcription factor, is one of the earliest cardiogenic markers. Although its expression continues through adulthood, its function in adult cardiomyocytes is not well understood. To examine the effect of Nkx2.5 in terminal differentiated postnatal cardiomyocytes, we generated transgenic mice expressing either wild-type Nkx2.5 (TG-wild), a putative transcriptionally active mutant (carboxyl-terminus deletion mutant: TG-ΔC) or a DNA non-binding point mutant of Nkx2.5 (TG-I183P) under α-myosin heavy chain promoter. Most TG-wild and TG-ΔC mice died before 4 months of age with heart failure associated with conduction abnormalities. Cardiomyocytes expressing wild-type Nkx2.5 or a putative transcriptionally active mutant (ΔC) had dramatically reduced expression of connexin 43 and changed sarcomere structure. Wild-type Nkx2.5 adenovirus-infected adult cardiomyocytes demonstrated connexin 43 downregulation as early as 16 h after infection, indicating that connexin 43 downregulation is due to Nkx2.5 overexpression but not due to heart failure phenotype in vivo. These studies indicate that overexpression of Nkx2.5 in terminally differentiated cardiomyocytes dramatically alters cardiac cell structure and function. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00222828
Volume :
35
Issue :
3
Database :
Academic Search Index
Journal :
Journal of Molecular & Cellular Cardiology
Publication Type :
Academic Journal
Accession number :
9405118
Full Text :
https://doi.org/10.1016/S0022-2828(03)00002-6