• neurodegenerative disease

Animals homozygous for amorphic mutations of the Drosophila microRNA gene mir-1000 exhibit progressive locomotor defects and sharply reduced adult lifespan; neuroanatomy defects and neurophysiology defects are observed in adult brain and larval neuromuscular junctions. These phenotypes are characteristic of fly models of neurodegenerative disease. The level of the mRNA of VGlut, one of many predicted targets of mir-1000, was shown to be significantly (~4-fold) increased in head preps of mir-1000 mutant animals. Reduction in the level of expression of VGlut rescues the phenotypes of the mir-1000 amorphic mutations.

mir-1000 is not found in mammals, however, there is a seed-similar microRNA, MIR137. A predicted target site of MIR137 is found in the 3' UTR of SLC17A6, one of three human orthologs of Dmel\VGlut. Both microRNAs, human MIR137 and Drosophila mir-1000, are able to regulate expression of a luciferase reporter transgene containing the human SLC17A6 3' UTR (assayed in S2 cells); this is no longer observed when the predicted seed site has been mutated. There is also a mir-137 microRNA in flies, which shows homology to human MIR137 in both the 5' seed region and along the full-length sequence (FBrf0215696).

Physical and genetic interactions of Dmel\mir-1000 have been described; see below and in the mir-1000 gene report. For fly transgenic constructs and classical alleles, detailed phenotypic descriptions can be found in the allele reports; allele reports can be accessed from the gene report or by clicking on the allele symbols in the Disease Ontology and Reagent tables below.

[updated Mar. 2018 by FlyBase; FBrf0222196]