Ballouhey Océane, Chapoton Marie, Alary Benedicte, Courrier Sébastien, Da Silva Nathalie, Krahn Martin, Lévy Nicolas, Weisleder Noah, Bartoli Marc
Aix Marseille University, INSERM, MMG, U1251, 13005 Marseille, France.
Département de Génétique Médicale et de Biologie Cellulaire, AP-HM, Hôpital d'Enfants de la Timone, 13005 Marseille, France.
Biomedicines. 2023 May 13;11(5):1438. doi: 10.3390/biomedicines11051438.
Dysferlinopathies are a group of autosomal recessive muscular dystrophies caused by pathogenic variants in the DYSF gene. While several animal models of dysferlinopathy have been developed, most of them involve major disruptions of the Dysf gene locus that are not optimal for studying human dysferlinopathy, which is often caused by single nucleotide substitutions. In this study, the authors describe a new murine model of dysferlinopathy that carries a nonsense mutation in Dysf exon 32, which has been identified in several patients with dysferlinopathy. This mouse model, called Dysf , displays several molecular, histological, and functional defects observed in dysferlinopathy patients and other published mouse models. This mutant mouse model is expected to be useful for testing various therapeutic approaches such as termination codon readthrough, pharmacological approaches, and exon skipping. Therefore, the data presented in this study strongly support the use of this animal model for the development of preclinical strategies for the treatment of dysferlinopathies.
肌膜蛋白病是一组由DYSF基因的致病变异引起的常染色体隐性肌肉营养不良症。虽然已经开发了几种肌膜蛋白病的动物模型，但其中大多数涉及Dysf基因座的重大破坏，这对于研究人类肌膜蛋白病并不理想，因为人类肌膜蛋白病通常由单核苷酸替换引起。在本研究中，作者描述了一种新的肌膜蛋白病小鼠模型，该模型在Dysf外显子32中携带无义突变，该突变已在数名肌膜蛋白病患者中被发现。这种称为Dysf的小鼠模型表现出在肌膜蛋白病患者和其他已发表的小鼠模型中观察到的几种分子、组织学和功能缺陷。这种突变小鼠模型有望用于测试各种治疗方法，如终止密码子通读、药理学方法和外显子跳跃。因此，本研究中呈现的数据有力地支持了使用这种动物模型来制定治疗肌膜蛋白病的临床前策略。
