In-vivo characterization of human dilated cardiomyopathy genes in zebrafish.
Due to lack of families suitable for linkage analysis and positional cloning most of the genetic causes of human dilated cardiomyopathy (DCM) are still unknown. To facilitate rapid identification and validation of novel DCM disease genes appropriate animal models are needed. To assess here for the first time whether the zebrafish is a suitable model organism to validate DCM candidate genes using antisense knock-down strategies, we inactivated in zebrafish known human DCM disease genes and then evaluated the resulting cardiac phenotypes. Consistently, knock-down of the here selected human DCM genes leads to severe heart failure with impairment of systolic cardiac function in zebrafish. Furthermore, gene-specific differences which are also seen in human DCM can be reliably reproduced in the zebrafish model. Our results indicate that the zebrafish is a suitable model organism to rapidly evaluate novel DCM disease genes in-vivo.
Vogel
Britta
B
Department of Medicine III, University of Heidelberg, Heidelberg, Germany.
Meder
Benjamin
B
Just
Steffen
S
Laufer
Christina
C
Berger
Ina
I
Weber
Sabrina
S
Katus
Hugo A
HA
Rottbauer
Wolfgang
W
D000595:Amino Acid Sequence; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure*; D015027:Zebrafish / Q000002:abnormalities / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
D029961:Zebrafish Proteins