Abstract
In humans, mutations in ZASP (the gene for Z-band alternatively spliced PDZ-motif protein) are associated with dilated cardiomyopathy and left ventricular non-compaction. In particular, mutations in or around the Zasp motif seem to be related to myofibrillar myopathy. Thus, “zaspopathies” include symptoms such as Z-line disgregation, proximal and distal muscle weakness, cardiomyopathies, and peripheral neuropathies. In order to understand the role of ZASP in muscle structure and function, we have performed a molecular characterization of the Drosophila ortholog of human ZASP and a functional analysis following the post-transcriptional silencing of the Drosophila gene. Transcriptional analysis of dzasp has revealed six additional exons, with respect to the known 16, and multiple splice variants. We have produced transgenic lines harboring constructs that, through the use of the UAS/Gal4 binary system, have enabled us to drive dsRNA interference of dzasp in a tissue-specific manner. Knockdown individuals show locomotor defects associated with alterations of muscle structure and ultrastructure, consistent with a role of dzasp specifically in the maintenance of muscular integrity.
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Acknowledgements
Thanks are due to Mr. M. Sturnega, ICGEB, Trieste, for excellent technical assistance in the immunization of the animals used for antibody production.
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The authors wish the first three authors to be regarded as joint first authors.
Financial support was provided by the Telethon Foundation, Italy (GGP04088 to G.F., GP0048Y01 to R.C.) and the Italian Centro Nazionale delle Ricerche and Ministero dell’Universita’ e della Ricerca “Legge 449/97” (CU04.00067 to R.C.)
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Benna, C., Peron, S., Rizzo, G. et al. Post-transcriptional silencing of the Drosophila homolog of human ZASP: a molecular and functional analysis. Cell Tissue Res 337, 463–476 (2009). https://doi.org/10.1007/s00441-009-0813-y
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DOI: https://doi.org/10.1007/s00441-009-0813-y