Calcineurin-induced cardiomyopathy has been modeled in Drosophila using one the three fly calcineurin catalytic subunit (CanA) genes, Pp2B-14D. Based primarily on studies in mice, it has been shown that calcineurin overactivity in the heart results in cardiomyopathy. Calcineurin is a calcium/calmodulin-dependent protein phosphatase that activates a wide range of substrates and is involved in multiple normal physiological processes, as well as a growing list of pathological conditions. Calcineurin consists of two subunits; in both human and flies there are multiple genes that encode each subunit. There are three CanA genes in human, PPP3CA, PPP3CB, and PPP3CC, and three in Drosophila, CanA-14F, Pp2B-14D, and CanA1. Amorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for all three fly genes.
UAS constructs of the wild-type human gene Hsap\PPP3CA have been introduced into flies, however they have not been used to investigate cardiomyopathy.
In adult flies, constitutively active Pp2B-14D in the heart results in heart enlargement, reduced cardiac contractility, and an increase in heart wall thickness. Genetics screens for modifiers of these phenotypes have been conducted. Physical and/or genetics interactions have been described for the three Drosophila CanA genes; see below and in the gene reports for Pp2B-14D, CanA-14F, and CanA1.
[updated Mar. 2017 by FlyBase; FBrf0222196]
See general reports for cardiomyopathy (FBhh0000508), hypertrophic cardiomyopathy (FBhh0000409), and dilated cardiomyopathy (FBhh0000134).
Calcineurin is a calcium/calmodulin-dependent protein phosphatase that consists of two subunits: a large calmodulin-binding catalytic subunit (CanA) and a small calcium-binding regulatory subunit (CanB). Calcineurin is involved in multiple physiological and pathological processes, including immune responses, neuronal plasticity, and cardiac development and hypertrophy (Sakuma and Yamaguchi, 2010; pubmed:20379369).
Many to many (3 human to 3 Drosophila). The three human genes are PPP3CA, PPP3CB, and PPP3CC.
Many to many (3 human to 3 Drosophila). The three human genes are PPP3CA, PPP3CB, and PPP3CC.
Many to many (3 human to 3 Drosophila). The three human genes are PPP3CA, PPP3CB, and PPP3CC.
High-scoring ortholog of human PPP3CA; moderate-scoring ortholog of PPP3CB and PPP3CC (3 Drosophila to 3 human). Dmel\Pp2B-14D shares 73-80% identity and 82-89% similarity with the human genes.
