Modulation of gene expression in transgenic mouse hearts overexpressing calsequestrin.
Calsequestrin (CSQ) is the major Ca2+ binding protein of the cardiac sarcoplasmic reticulum (SR). Transgenic mice overexpressing CSQ at the age of 7 weeks exhibit concentric cardiac hypertrophy, and by 13 weeks the condition progresses to dilated cardiomyopathy. The present study used a differential display analysis to identify genes whose expressions are modulated in the CSQ-overexpressing mouse hearts to provide information on the mechanism of transition from concentric cardiac hypertrophy to failure. Cardiac ankyrin repeat protein (CARP), glutathione peroxidase (Gpx1), and genes which participate in the formation of extracellular matrix including decorin, TSC-36, Magp2, Osf2, and SPARC are upregulated in CSQ mouse hearts at 7 and 13 weeks of age compared to those of non-transgenic littermates. In addition, two novel genes without sequence similarities to any known genes are upregulated in CSQ-overexpressing mouse hearts. Several genes are downregulated at 13 weeks, including SR Ca2+-ATPase (SERCA2) and adenine nucleotide translocase 1 (Ant1) genes. Further, a functionally yet unknown gene (NM_026586) previously identified in the mouse wolffian duct is dramatically downregulated in CSQ mice with dilated hearts. Thus, CARP, Gpx1, and genes encoding extracellular matrix proteins may participate in the development of cardiac hypertrophy and fibrosis, and changes in SERCA2, Ant1, and NM_026586 mRNA expression may be involved in transition from concentric to dilated cardiac hypertrophy.
Ihara
Y
Y
Hokkaido Food Processing Research Center, Ebetsu, 069-0836 Hokkaido, Japan.
Suzuki
Y J
YJ
Kitta
K
K
Jones
L R
LR
Ikeda
T
T
D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002155:Calsequestrin / Q000235:genetics*; D006332:Cardiomegaly / Q000235:genetics* / Q000503:physiopathology*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000235:genetics; D006321:Heart / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
D033741:Adenine Nucleotide Translocator 1; C104844:Ankrd1 protein, mouse; D002155:Calsequestrin; D016326:Extracellular Matrix Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005979:Glutathione Peroxidase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D000252:Calcium-Transporting ATPases; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse