Introduction of disease-associated mutations in Drosophila orthologs of genes linked to myopathy and muscular dystrophy

Li S, Zhang P, Freibaum BD, Kim NC, Kolaitis RM, Molliex A, Kanagaraj AP, Yabe I, Tanino M, Tanaka S, Sasaki H, Ross ED, Taylor JP, Kim HJ. Genetic interaction of hnRNPA2B1 and DNAJB6 in a Drosophila model of multisystem proteinopathy. Hum Mol Genet. 2016 Mar 1;25(5):936-50. PMID: 26744327; PMCID: PMC4754048.

From the abstract: "Adult-onset inherited myopathies with similar pathological features, including hereditary inclusion body myopathy (hIBM) and limb-girdle muscular dystrophy (LGMD), are a genetically heterogeneous group of muscle diseases. ... Here, we exploit a genetic model system to establish a mechanistic link between diseases caused by mutations in two distinct genes, hnRNPA2B1 and DNAJB6. Hrb98DE and mrj are the Drosophila melanogaster homologs of human hnRNPA2B1 and DNAJB6, respectively. We introduced disease-homologous mutations to Hrb98DE, thus capturing mutation-dependent phenotypes in a genetically tractable model system. ... These results indicate both genetic and physical interactions between disease-linked RBPs and DNAJB6/mrj, suggesting etiologic overlap between the pathogenesis of hIBM and LGMD initiated by mutations in hnRNPA2B1 and DNAJB6."

New fly model of Inclusion Body Myopathy 3. Recent report.

This study describes a new fly model based on introduction of a human disease-associated missense mutation (E706K) in myosin heavy chain IIa. The mutant form was introduced via P-element transformation and crossed into an Mhc null mutant background.

Wang Y, Melkani GC, Suggs JA, Melkani A, Kronert WA, Cammarato A, Bernstein SI. Expression of the inclusion body myopathy 3 mutation in Drosophila depresses myosin function and stability and recapitulates muscle inclusions and weakness. Mol Biol Cell. 2012 Jun;23(11):2057-65. Epub 2012 Apr 11. PubMed PMID: 22496423; PubMed Central PMCID: PMC3364171.