Wednesday, September 22, 2021

Fly disease model of Limb-girdle muscular dystrophy D2 (LGMDDs)

Blázquez-Bernal Á, Fernandez-Costa JM, Bargiela A, Artero R. Inhibition of autophagy rescues muscle atrophy in a LGMDD2 Drosophila model. FASEB J. 2021 Oct;35(10):e21914. doi: 10.1096/fj.202100539RR. PMID: 34547132.

From the abstract: "Limb-girdle muscular dystrophy D2 (LGMDD2) is an ultrarare autosomal dominant myopathy caused by mutation of ... TNPO3 ... . ... Here we report the first animal model of the disease by expressing the human mutant TNPO3 gene in Drosophila musculature or motor neurons and concomitantly silencing the endogenous expression of the fly protein ortholog. A similar genotype expressing wildtype TNPO3 served as a control. Phenotypes characterization revealed that mutant TNPO3 expression targeted at muscles or motor neurons caused LGMDD2-like phenotypes such as muscle degeneration and atrophy, and reduced locomotor ability. ... Upregulated muscle autophagy observed in LGMDD2 patients was also confirmed in the fly model, in which the anti-autophagic drug chloroquine was able to rescue histologic and functional phenotypes. Overall, we provide a proof of concept of autophagy as a target to treat disease phenotypes and propose a neurogenic component to explain mutant TNPO3 pathogenicity in diseased muscles."

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