This report describes a fly model of diseases related to overactivity of the gene glycogen synthase 1 (GYS1), also known as muscle glycogen synthase (MGS). Aberrant glycogen accumulation is observed in a number of disease, notably in neurons in patients suffering from Lafora disease (myoclonic epilepsy of Lafora; MIM:254780). GYS1 catalyzes the addition of glucose monomers during the synthesis of glycogen. There is a single fly ortholog, Dmel\GlyS, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\GlyS is orthologous to an additional human gene, GYS2. GYS1 is also implicated in muscle glycogen storage disease-0 (MIM:611556), which is associated with loss of function or deficiency for GYS1.
Several UAS construct of the human Hsap\GYS1 gene have been introduced into flies, including wild-type and a constitutively active form; heterologous rescue has not been tested. The constitutively active variant, which is resistant to inactivation by phosphorylation, produces more extreme phenotypes. When expressed in neurons, phenotypes include reduction in lifespan and locomotion defects.
Genetic characterization of the Drosophila GlyS gene is very limited. Physical interactions of the GlyS protein product have been described; see below and in the FlyBase gene report for GlyS.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Aberrant glycogen accumulation in neurons is a common finding in patients suffering from Lafora progressive myoclonic epilepsy and other polyglucosan disorders.
Glycogen synthase 1 (GYS1), also known as muscle glycogen synthase (MGS), catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages. [from Gene Cards, GYS1; 2016.05.23]
Many to one: 2 human to 1 Drosophila; the fly gene GlyS is orthologous to GYS1 and GYS2 in human.
High-scoring ortholog of human genes GYS1 and GYS2 (1 Drosophila to 2 human). Dmel\GlyS shares 58-59% identity and 76% similarity with the human genes.
