Characterization of the frameshift c.515dupC knock-in mouse model of HSPB8-associated myopathy (MFM13) and evaluation of Trehalose as autophagy modulating therapy.

Hspb8 c.515dupC knock-in mice develop late-onset muscle weakness starting at 15 months, with reduced HSPB8, increased TDP-43, and altered autophagy markers.

• Why it matters: HSPB8-associated MFM13 lacks effective treatments, and patient data show disrupted CASA-linked autophagy and TDP-43 accumulation that need mechanistic and therapeutic testing in vivo.
• What they did: Using CRISPR, the authors generated the c.515dupC frameshift knock-in mouse and assessed muscle weakness, HSPB8/TDP-43 levels, and autophagy markers, then tested 2% trehalose in drinking water.
• The result: Trehalose restored HSPB8 expression but did not significantly improve autophagic dysfunction or TDP-43 pathology in mutant mice, supporting the model’s translational value while challenging autophagy enhancement alone.

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