Targeted disruption of the mouse Csrp2 gene encoding the cysteine- and glycine-rich LIM domain protein CRP2 result in subtle alteration of cardiac ultrastructure.
BACKGROUND
The cysteine and glycine rich protein 2 (CRP2) encoded by the Csrp2 gene is a LIM domain protein expressed in the vascular system, particularly in smooth muscle cells. It exhibits a bimodal subcellular distribution, accumulating at actin-based filaments in the cytosol and in the nucleus. In order to analyze the function of CRP2 in vivo, we disrupted the Csrp2 gene in mice and analysed the resulting phenotype.


RESULTS
A approximately 17.3 kbp fragment of the murine Csrp2 gene containing exon 3 through 6 was isolated. Using this construct we confirmed the recently determined chromosomal localization (Chromosome 10, best fit location between markers D10Mit203 proximal and D10Mit150 central). A gene disruption cassette was cloned into exon 4 and a mouse strain lacking functional Csrp2 was generated. Mice lacking CRP2 are viable and fertile and have no obvious deficits in reproduction and survival. However, detailed histological and electron microscopic studies reveal that CRP2-deficient mice have subtle alterations in their cardiac ultrastructure. In these mice, the cardiomyocytes display a slight increase in their thickness, indicating moderate hypertrophy at the cellular level. Although the expression of several intercalated disc-associated proteins such as beta-catenin, N-RAP and connexin-43 were not affected in these mice, the distribution of respective proteins was changed within heart tissue.


CONCLUSIONS
We conclude that the lack of CRP2 is associated with alterations in cardiomyocyte thickness and hypertrophy.
Sagave
Julia F
JF
Institute of Clinical Chemistry and Pathobiochemistry, RWTH- University Hospital Aachen, Germany. julia.sagave@gmx.de
Moser
Markus
M
Ehler
Elisabeth
E
Weiskirchen
Sabine
S
Stoll
Doris
D
Günther
Kalle
K
Büttner
Reinhard
R
Weiskirchen
Ralf
R
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting; D005822:Genetic Vectors; D005838:Genotype; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D010957:Plasmids; D012313:RNA / Q000235:genetics; D021101:Radiation Hybrid Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction
C484376:Csrp2 protein, mouse; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012313:RNA