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Citation
Akasaka, T., Ocorr, K., Lin, L., Vogler, G., Bodmer, R., Grossfeld, P. (2020). Overexpression of Kif1A in the Developing Drosophila Heart Causes Valvar and Contractility Defects: Implications for Human Congenital Heart Disease.  J. Cardiovasc. Dev. Dis. 7(2): E22.
FlyBase ID
FBrf0245862
Publication Type
Research paper
Abstract

Left-sided congenital heart defects (CHDs) are among the most common forms of congenital heart disease, but a disease-causing gene has only been identified in a minority of cases. Here, we identified a candidate gene for CHDs, KIF1A, that was associated with a chromosomal balanced translocation t(2;8)(q37;p11) in a patient with left-sided heart and aortic valve defects. The breakpoint was in the 5' untranslated region of the KIF1A gene at 2q37, which suggested that the break affected the levels of Kif1A gene expression. Transgenic fly lines overexpressing Kif1A specifically in the heart muscle (or all muscles) caused diminished cardiac contractility, myofibrillar disorganization, and heart valve defects, whereas cardiac knockdown had no effect on heart structure or function. Overexpression of Kif1A also caused increased collagen IV deposition in the fibrous network that normally surrounds the fly heart. Kif1A overexpression in C2C12 myoblasts resulted in specific displacement of the F-actin fibers, probably through a direct interaction with G-actin. These results point to a Kif1A-mediated disruption of F-actin organization as a potential mechanism for the pathogenesis in at least some human CHDs.

PubMed ID
PubMed Central ID
PMC7345553 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cardiovasc. Dev. Dis.
    Title
    Journal of cardiovascular development and disease
    ISBN/ISSN
    2308-3425
    Data From Reference
    Aberrations (2)
    Alleles (10)
    Genes (3)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (3)
    Transgenic Constructs (9)