中国实验动物学报2025，Vol.33Issue(7)：968-979,12.DOI:10.3969/j.issn.1005-4847.2025.07.004
一种新型面肩肱肌营养不良症小鼠模型的建立
A new mouse model of facioscapulohumeral muscular dystrophy
摘要
Abstract
Objective To establish a transgenic mouse model of facioscapulohumeral muscular dystrophy(FSHD)using tamoxifen induction and Myf6-CreERT2 and FLExDUX4 mice.Methods Dual transgenic(M6D4/+)mice were generated by crossbreeding Myf6-CreERT2 hemizygous and FLExDUX4 hemizygous mice.Full-length DUX4(DUX4-fl)expression was induced by tamoxifen starting at 3 weeks old.The disease model was evaluated at 9 weeks old by assessing changes in body mass,four-limb strength,inverted screen test,skeletal muscle weight ratio,hematoxylin/eosin,Picrosirius Red,and immunofluorescent staining of skeletal muscle paraffin sections,quantitative real-time polymerase chain reaction(RT-PCR),and RNA-sequencing(RNA-seq)of skeletal muscle.Results Dual transgenic heterozygous mice(M6D4/+)were successfully obtained.These mice exhibited significant physiological and pathological changes at 9 weeks,including delayed weight gain,reduced four-limb strength and endurance,decreased skeletal muscle weight ratio,and increases in centrally nucleated muscle fibers and fibrosis.Expression levels of DUX4 and its targeted genes were significantly up-regulated in skeletal muscle,as demonstrated by RT-PCR.RNA-seq revealed up-regulation of immune regulation-,interleukin-6,and tumor necrosis factor-related genes and down-regulation of skeletal muscle development-and differentiation-related genes.Conclusions M6D4/+mice effectively simulated the skeletal muscle phenotype of FSHD and thus provide a good animal model for research into the pathogenesis,intervention,and treatment of FSHD.关键词
面肩肱肌营养不良症/DUX4/Myf6/骨骼肌/小鼠模型Key words
facioscapulohumeral muscular dystrophy/DUX4/Myf6/skeletal muscle/mouse model分类
生物科学引用本文复制引用
陈昊,孟茹,蒋凌东,刘雯雯,安君,吴思惠,张沁欣,张军,胡平..一种新型面肩肱肌营养不良症小鼠模型的建立[J].中国实验动物学报,2025,33(7):968-979,12.基金项目
国家自然科学基金(81971398).Funded by the National Natural Science Foundation of China(81971398). （81971398）
