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Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.

Publication ,  Journal Article
Casad, ME; Yu, L; Daniels, JP; Wolf, MJ; Rockman, HA
Published in: Mol Genet Genomics
April 2012

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.

Duke Scholars

Published In

Mol Genet Genomics

DOI

EISSN

1617-4623

Publication Date

April 2012

Volume

287

Issue

4

Start / End Page

351 / 360

Location

Germany

Related Subject Headings

  • Signal Transduction
  • Repressor Proteins
  • RNA-Binding Proteins
  • RNA Splicing Factors
  • Plant Biology & Botany
  • Male
  • Humans
  • Genetics & Heredity
  • Gene Deletion
  • Female
 

Citation

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Casad, M. E., Yu, L., Daniels, J. P., Wolf, M. J., & Rockman, H. A. (2012). Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy. Mol Genet Genomics, 287(4), 351–360. https://doi.org/10.1007/s00438-012-0684-x
Casad, Michelle E., Lin Yu, Joseph P. Daniels, Matthew J. Wolf, and Howard A. Rockman. “Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.Mol Genet Genomics 287, no. 4 (April 2012): 351–60. https://doi.org/10.1007/s00438-012-0684-x.
Casad ME, Yu L, Daniels JP, Wolf MJ, Rockman HA. Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy. Mol Genet Genomics. 2012 Apr;287(4):351–60.
Casad, Michelle E., et al. “Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.Mol Genet Genomics, vol. 287, no. 4, Apr. 2012, pp. 351–60. Pubmed, doi:10.1007/s00438-012-0684-x.
Casad ME, Yu L, Daniels JP, Wolf MJ, Rockman HA. Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy. Mol Genet Genomics. 2012 Apr;287(4):351–360.
Journal cover image

Published In

Mol Genet Genomics

DOI

EISSN

1617-4623

Publication Date

April 2012

Volume

287

Issue

4

Start / End Page

351 / 360

Location

Germany

Related Subject Headings

  • Signal Transduction
  • Repressor Proteins
  • RNA-Binding Proteins
  • RNA Splicing Factors
  • Plant Biology & Botany
  • Male
  • Humans
  • Genetics & Heredity
  • Gene Deletion
  • Female