A new mouse model of facioscapulohumeral muscular dystrophy
10.3969/j.issn.1005-4847.2025.07.004
- VernacularTitle:一种新型面肩肱肌营养不良症小鼠模型的建立
- Author:
Hao CHEN
1
;
Ru MENG
;
Lingdong JIANG
;
Wenwen LIU
;
Jun AN
;
Sihui WU
;
Qinxin ZHANG
;
Jun ZHANG
;
Ping HU
Author Information
1. 南京医科大学附属妇产医院(南京市妇幼保健院),南京 210004
- Publication Type:Journal Article
- Keywords:
facioscapulohumeral muscular dystrophy;
DUX4;
Myf6;
skeletal muscle;
mouse model
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(7):968-979
- CountryChina
- Language:Chinese
-
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.
