DOI: 10.1002/ame2.70063
Development,validation,and preliminary phenotypic characterization of a Col6a3 knockout mouse model targeting exon 3
Michel ElChoueiry
Harsimran Sidhu
Maude Lévesque
Dominique Lévesque
Jean-François Jacques
Otman Sarrhini
Jean-François Beaudoin
Molly Caron
Brenda Gaudette
Roger Lecomte
Xavier Roucou
François-Michel Boisvert
Jean-Philippe Brosseau
Abstract：Background: Most mutations in the COL6A3 gene lead to collagen VI-related myopathies. This is due to a reduced expression or mislocalization of the COL6A3 protein. Therefore, studying the consequence of knocking out the Col6a3 gene in mouse models is relevant, but the Col6a3 mouse models reported so far do not entirely abolish COL6A3 protein expression.
Methods: Here, we present the development, validation and preliminary phenotypic characterization of a novel CRISPR-based knockout mouse model targeting Col6a3 exon 3 (Col6a3d3/d3).
Results: In this mouse model, Col6a3 mRNA is still expressed at a similar level to wild-type littermates, although the expected protein is undetectable by mass spectrometry. Histological analysis of Col6a3d3/d3 quadriceps revealed an abnormally high frequency of muscle cells with internally nucleated muscle cells, consistent with a myopathy phenotype. Interestingly, Col6a3d3/d3 mice are smaller in size, with their fat, muscle, and bone kept proportional compared to wild-type littermates.
Conclusions: In summary, we performed the validation and preliminary phenotypic characterization of a novel Col6a3 knockout mouse model that could be further characterized and used to study COL6A3 biology and model collagen VI-associated diseases.
Keywords：collagen ⅥCRISPRmass spectrometrymouse model of human diseasemyopathy
Publication Date：2025-10-30
Online Publishing Date：2025-12-16(First online date of this platform, not the publication date of the document)
Pages：12( 1824-1835 )