Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice.
A cardiac homeobox-containing gene Csx/Nkx2-5, which is essential for cardiac development, is abundantly expressed in the adult heart as well as in the heart primordia. Targeted disruption of this gene results in embryonic lethality due to abnormal heart morphogenesis. To elucidate the role of Csx/Nkx2-5 in the adult heart, we generated transgenic mice which overexpress human Csx/Nkx2-5. The transgene was expressed abundantly in the heart and the skeletal muscle. mRNA levels of several cardiac genes including natriuretic peptides, CARP, MLC2v, and endogenous Csx/Nkx2-5 were increased in the ventricle of the transgenic mice. Electron microscopic analysis revealed that the ventricular myocardium of the transgenic mice had many secretory granules, which disappeared after administration of vasopressin. These results suggest that Csx/Nkx2-5 regulates many cardiac genes and induces formation of secretory granules in the adult ventricle.
Takimoto
E
E
Department of Cardiovascular Medicine, Department of Hematology and Oncology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Mizuno
T
T
Terasaki
F
F
Shimoyama
M
M
Honda
H
H
Shiojima
I
I
Hiroi
Y
Y
Oka
T
T
Hayashi
D
D
Hirai
H
H
Kudoh
S
S
Toko
H
H
Kawamura
K
K
Nagai
R
R
Yazaki
Y
Y
Komuro
I
I
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D024722:Cardiac Myosins; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology; D006352:Heart Ventricles; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins
C491304:ANKRD1 protein, human; C104844:Ankrd1 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C107184:myosin light chain 2; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D024722:Cardiac Myosins