DOI: 10.1002/ame2.70063
Development,validation,and preliminary phenotypic characterization of a Col6a3 knockout mouse model targeting exon 3
Michel ElChoueiry1
Harsimran Sidhu1
Maude Lévesque1
Dominique Lévesque2
Jean-François Jacques1
Otman Sarrhini3
Jean-François Beaudoin3
Molly Caron1
Brenda Gaudette1
Roger Lecomte4
Xavier Roucou5
François-Michel Boisvert6
Jean-Philippe Brosseau5
1.Department of Biochemistry and Functional Genomic,Université de Sherbrooke,Sherbrooke,Quebec,Canada2.Department of Immunology and Cellular Biology,Université de Sherbrooke,Sherbrooke,Quebec,Canada3.Centre d'Imagerie Moléculaire de Sherbrooke du Centre de Recherche du Centre Hospitalier,Universitaire de Sherbrooke,Sherbrooke,Quebec,Canada4.Centre d'Imagerie Moléculaire de Sherbrooke du Centre de Recherche du Centre Hospitalier,Universitaire de Sherbrooke,Sherbrooke,Quebec,Canada;Department of Nuclear Medicine and Radiobiology,Université de Sherbrooke,Sherbrooke,Quebec,Canada5.Department of Biochemistry and Functional Genomic,Université de Sherbrooke,Sherbrooke,Quebec,Canada;Institut de Recherche sur le Cancer de l'Université de Sherbrooke,Sherbrooke,Quebec,Canada6.Department of Immunology and Cellular Biology,Université de Sherbrooke,Sherbrooke,Quebec,Canada;Institut de Recherche sur le Cancer de l'Université de Sherbrooke,Sherbrooke,Quebec,Canada
摘要：Background:Most mutations in the COL6A3 gene lead to collagen Ⅵ-related myopa-thies.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 mod-els 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 spec-trometry.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 charac-terized and used to study COL6A3 biology and model collagen Ⅵ-associated diseases.
机标关键词：developmentknockoutmousemodelexoncharacterphenotypicpreliminary
论文发表日期：2025-10-30
在线出版日期：2025-12-16（本平台首次上网日期，不代表文献的发表时间）
页数：12( 1824-1835 )
英文信息