Col6a1 knock-in mice provide a promising pre-clinical model for collagen VI-related dystrophies.

ABSTRACT: Collagen VI related dystrophies (COL6-RD) are congenital muscle diseases, typically inherited as an autosomal dominant trait. A frequent type of pathogenic variant involves glycine substitutions in the triple helical domain of collagen VI alpha chains, exerting a dominant-negative effect on the unaltered protein. Despite this, no prior animal model captured this mutation type. By using CRISPR/Cas9, we generated transgenic mice with the equivalent of the human COL6A1 c.877 G>A; p. Gly293Arg pathogenic variant. We characterized their skeletal muscle phenotype over time, utilizing computer-aided tools applied to standardized parameters of muscle pathology and function. Knock-in mice exhibited early-onset reduced muscle weight, myopathic histology, increased fibrosis, reduced collagen VI expre

SUBMITTER: Lopez-Marquez A 

PROVIDER: S-EPMC12869505 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature