RRC ID 74640
著者 Kodani A, Yamaguchi M, Itoh R, Huynh MA, Yoshida H.
タイトル A Drosophila model of the neurological symptoms in Mpv17-related diseases.
ジャーナル Sci Rep
Abstract Mutations in the Mpv17 gene are responsible for MPV17-related hepatocerebral mitochondrial DNA depletion syndrome and Charcot-Marie-Tooth (CMT) disease. Although several models including mouse, zebrafish, and cultured human cells, have been developed, the models do not show any neurological defects, which are often observed in patients. Therefore, we knocked down CG11077 (Drosophila Mpv17; dMpv17), an ortholog of human MPV17, in the nervous system in Drosophila melanogaster and investigated the behavioral and cellular phenotypes. The resulting dMpv17 knockdown larvae showed impaired locomotor activity and learning ability consistent with mitochondrial defects suggested by the reductions in mitochondrial DNA and ATP production and the increases in the levels of lactate and reactive oxygen species. Furthermore, an abnormal morphology of the neuromuscular junction, at the presynaptic terminal, was observed in dMpv17 knockdown larvae. These results reproduce well the symptoms of human diseases and partially reproduce the phenotypes of Mpv17-deficient model organisms. Therefore, we suggest that neuron-specific dMpv17 knockdown in Drosophila is a useful model for investigation of MPV17-related hepatocerebral mitochondrial DNA depletion syndrome and CMT caused by Mpv17 dysfunction.
巻・号 12(1)
ページ 22632
公開日 2022-12-31
DOI 10.1038/s41598-022-27329-x
PII 10.1038/s41598-022-27329-x
PMID 36587049
PMC PMC9805426
MeSH Animals DNA, Mitochondrial / genetics Drosophila* / genetics Drosophila melanogaster* / genetics Humans Membrane Proteins / genetics Mice Mitochondrial Proteins / genetics Mutation Zebrafish / genetics
IF 3.998
リソース情報
ショウジョウバエ DGRC#108479 DGRC#101249