This report describes neuromuscular disease, MARS2-related, which includes diseases associated with the human gene MARS2, a nuclear gene that encodes a mitochondrial methionyl-tRNA synthetase protein. There is a single fly ortholog, MetRS-m, for which loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Lesions in MARS2 that result in symptoms of spastic ataxia 3 (OMIM:611390; FBhh0000448) usually involve genomic rearrangements. Based on one family, compound heterozygous (recessive) mutation of MARS2 has been implicated in combined oxidative phosphorylation deficiency 1 (OMIM:616430).
UAS constructs of the human gene, Hsap\MARS2, have been introduced into flies; heterologous rescue (functional complementation) has been demonstrated.
Missense mutations of Dmel\MetRS-m were initially isolated as part of a screen for mutations causing aberrant electroretinograms that significantly worsen with age, indicating degeneration of photoreceptors. Animals homozygous for these alleles have shorter lifespans than wild-type flies and are unable to fly. Myofibrils in the indirect flight muscles exhibit a mitochondrial defect which leads to progressive degeneration of the muscle. More severe genotypes (missense mutation over deficiency) are lethal during larval and pupal stages. Physical interactions of Dmel\MetRS-m have been described; see below and in the gene report for MetRS-m.
[updated Jul. 2017 by FlyBase; FBrf0222196]