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Molecular Genetics and Genomics

, Volume 287, Issue 4, pp 351–360 | Cite as

Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy

  • Michelle E. Casad
  • Lin Yu
  • Joseph P. Daniels
  • Matthew J. Wolf
  • Howard A. RockmanEmail author
Original Paper

Abstract

Drosophila is a useful model organism in which the genetics of human diseases, including recent advances in identification of the genetics of heart development and disease in the fly, can be studied. To identify novel genes that cause cardiomyopathy, we performed a deficiency screen in adult Drosophila. Using optical coherence tomography to phenotype cardiac function in awake adult Drosophila, we identified Df(1)Exel6240 as having cardiomyopathy. Using a number of strategies including customized smaller deletions, screening of mutant alleles, and transgenic rescue, we identified CG3226 as the causative gene for this deficiency. CG3226 is an uncharacterized gene in Drosophila possessing homology to the mammalian Siah-interacting protein (SIP) gene. Mammalian SIP functions as an adaptor protein involved in one of the β-catenin degradation complexes. To investigate the effects of altering β-catenin/Armadillo signaling in the adult fly, we measured heart function in flies expressing either constitutively active Armadillo or transgenic constructs that block Armadillo signaling, specifically in the heart. While, increasing Armadillo signaling in the heart did not have an effect on adult heart function, decreasing Armadillo signaling in the fly heart caused the significant reduction in heart chamber size. In summary, we show that deletion of CG3226, which has homology to mammalian SIP, causes cardiomyopathy in adult Drosophila. Alterations in Armadillo signaling during development lead to important changes in the size and function of the adult heart.

Keywords

Drosophilamelanogaster Cardiomyopathy Siah-interacting protein (SIP) Armadillo/β-catenin 

Notes

Acknowledgments

This work was supported by grants from the National Institutes of Health HL-083965 to H.A.R., HL085072 to M.J.W, and the American Heart Association predoctoral fellowships 0715314U and 09PRE2110019 to M.E.C.

Supplementary material

438_2012_684_MOESM1_ESM.pdf (1.4 mb)
Supplementary material 1 (PDF 1442 kb)
438_2012_684_MOESM2_ESM.pdf (608 kb)
Supplementary material 2 (PDF 608 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Michelle E. Casad
    • 1
  • Lin Yu
    • 2
  • Joseph P. Daniels
    • 2
  • Matthew J. Wolf
    • 2
  • Howard A. Rockman
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Cell BiologyDuke University Medical CenterDurhamUSA
  2. 2.Department of MedicineDuke University Medical CenterDurhamUSA
  3. 3.Department of Molecular Genetics and MicrobiologyDuke University Medical CenterDurhamUSA

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