Key result
Overexpression of the E3-ligase Abba/Thin fully suppressed the impaired jump and flight ability and myopathy associated with the MhcK1728del mutation in a Drosophila model of Laing distal myopathy.
Why the study?
Does overexpression of a TRIM-protein family member alleviate pathological phenotypes in a Drosophila model of MYH7-associated myosin myopathy?
Does overexpression of a TRIM-protein family member alleviate pathological phenotypes in a Drosophila model of MYH7-associated myosin myopathy?
p-value: p=<0.0001
Overexpression of a TRIM-protein family member rescues the pathological phenotype in a Drosophila model of MYH7-associated myosin myopathy, suggesting E3-ligase activity may modify disease severity in patients.
E3-ligase overexpression rescues Drosophila myosin myopathy phenotypes; hypothesis-generating, translation to human MYH7 disease untested.
Significance The majority of mutations residing within the rod domain of myosin have been associated with skeletal myopathy with or without cardiomyopathy. However, the molecular mechanisms underlying the variation in clinical and pathological phenotypes of myopathies associated with the MYH7 mutation are still poorly understood. We used CRISPR/Cas9-mediated genome engineering to develop a fly model for Laing distal myopathy to investigate the pathological mechanisms of the recurrent L1729del MYH7 mutation. This study unveils structural and functional phenotypes associated with this mutation in skeletal and heart muscles, and identifies a mechanism that alleviates the pathological phenotype, suggesting that E3-ligase modifier gene activity may reduce or enhance the impact of this myosin mutation in patients.
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Dahl-Halvarsson et al. (2018) studied Laing distal myopathy (Drosophila model). Overexpression of Abba/Thin vs. MhcK1728del mutants without Abba overexpression was evaluated on Jump and flight ability and muscle morphology (p=<0.0001). Overexpression of the E3-ligase Abba/Thin fully suppressed the impaired jump and flight ability and myopathy associated with the MhcK1728del mutation in a Drosophila model of Laing distal myopathy.
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