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FB2026_01
,
released March 12, 2026
Intrauterine growth restriction (IUGR) in humans can be caused by a number of factors, one of which is prenatal abnormalities in insulin-like growth factor signaling. Symmetrical IUGR is associated with global growth restriction, decreased cell proliferation, significant lethality at birth, and learning defects. Mutations in the chico gene in Drosophila, the single fly ortholog of the human insulin receptor substrate genes (IRS1, IRS2, IRS4), result in the same repertoire of phenotypes. Classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\chico.
None of the human insulin receptor substrate genes has been introduced into flies.
Animals homozygous for an amorphic mutation of chico have lower body weight, fewer ommatidia, smaller wings, and fewer cells per wing than wild type; they exhibit learning defects and females are sterile. It has been shown that chico mutations disrupt olfactory associative learning, at least in part, by reducing cAMP signaling in specific parts of the brain and that this phenotype can be rescued by overexpression of a downstream adenylyl cyclase gene. Thus, it is postulated that cognitive defects associated with IUGR related to reduced insulin signaling may occur from acute reductions in cAMP signaling, independently of developmental defects. Many genetic and physical interactions of Dmel\chico have been described; see below and in the chico gene report.
[updated Sep. 2017 by FlyBase; FBrf0222196]
Intrauterine growth restriction (IUGR) has been defined as a rate of fetal growth that is below normal in light of the growth potential of a specific infant as per the race and gender of the fetus (Sharma et al., 2016; pubmed:27441006).
Impaired fetal growth increases the risk of later diabetes and impaired glucose tolerance. Some of this association between birth weight and diabetes may reflect the effect of genetic polymorphisms which reduce insulin action in fetal life as well as after birth (Gatford and Simmons, 2014; pubmed:23820120).
Mutations in the chico gene in Drosophila and symmetrical IUGR in humans are associated with several similar phenotypes, including decreased cell proliferation, global growth restriction, significant lethality at birth, and learning defects.
In flies, chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in specific parts of the brain. Thus, cognitive defects associated with reduced insulin signaling may occur from acute reductions in cAMP signaling, independently of developmental defects.
Many to one: 3 human to 1 Drosophila; the human genes are IRS1, IRS2, IRS4.
Many to one: 3 human to 1 Drosophila; the human genes are IRS1, IRS2, IRS4.
Many to one: 3 human to 1 Drosophila; the human genes are IRS1, IRS2, IRS4.
Moderate-scoring ortholog of human IRS1, IRS2, IRS4 (1 Drosophila to 3 human). Dmel\chico shares 21-23% identity and 34-37% similarity with the human genes.