Knock-in mouse model of HSPB8-linked myopathy characterised; trehalose evaluated as autophagy therapy

Researchers have posted a preprint to bioRxiv reporting characterisation of a knock-in mouse model carrying the c.515dupC frameshift mutation in HSPB8, the gene encoding heat shock protein family B member 8. This mutation was recently linked to an autosomal dominant rimmed vacuolar myopathy designated MFM13 (myofibrillar myopathy type 13), which presents with distal and proximal limb-girdle weakness and muscle biopsy findings including fatty replacement. HSPB8 was previously associated with Charcot–Marie–Tooth disease type 2L, and is also considered relevant to a broader spectrum of multisystem proteinopathies.

HSPB8 functions as a chaperone within the chaperone-assisted selective autophagy (CASA) complex, working alongside co-chaperone BAG3 to direct misfolded proteins for autophagic degradation. The frameshift mutation is predicted to disrupt this function. The preprint describes the myopathic phenotype observed in homozygous knock-in mice and evaluates trehalose — a disaccharide known to modulate autophagy — as a potential therapeutic strategy in this model.

The study has not yet undergone peer review. It will be of primary interest to researchers working on rare hereditary myopathies, neuromuscular disease, and autophagy biology, as well as genetic counsellors involved with MFM13-affected families and educators covering inherited muscle disease. The work also illustrates the value of genetically precise animal models for rare autosomal dominant conditions.