Phenotypic characterization of a Col6a3 knockout mouse model targeting exon 3

ABSTRACT: Mutations in COL6A3 lead to collagen VI-related myopathies due to COL6A3 loss. Therefore, studying the consequence of Col6a3 deregulated expression in mouse models is relevant, but the Col6a3 knockout mouse models currently available through a public repository does not entirely abolish COL6A3 protein expression. Here, we present the validation and phenotypic characterization of a novel CRISPR-based knockout mouse model targeting Col6a3 exon 3 (Col6a3 d3/d3). In this mouse model, Col6a3 mRNA is still expressed at a similar level to that of wild-type littermates, although the expected protein is undetectable. Histological analysis of Col6a3 d3/d3 quadriceps revealed an abnormally high frequency of muscle cells with a centralized nuclei, consistent with a muscular dystrophy phenotype. Interestingly, Col6a3 d3/d3 mice are smaller in size with their fat, muscle, and bone to body ratios kept proportional compared to wild type littermates. Thus, we developed a novel Col6a3 knockout mouse model that could be further used to study Col6a3 biology and collagen VI-associated diseases.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epidermal Cell, Skin

SUBMITTER: Dominique Levesque  

LAB HEAD: Jean-Philippe Brosseau

PROVIDER: PXD057310 | Pride | 2025-12-08

REPOSITORIES: Pride