Key result
Four of five offspring carrying the DNM2 c.1393C>T mutation showed muscle atrophy, mildly impaired gait, and CNM-typical fibres with centralized nuclei, establishing a faithful dog model for ADCNM.
Why the study?
To establish a large animal model for longitudinal and preclinical studies on autosomal dominant centronuclear myopathy.
Answers are grounded in this paper and cite their sources.
Spontaneous canine ADCNM model identified; leaves open validation for cross-species mechanistic and therapeutic studies.
Mutations in DNM2 cause autosomal dominant centronuclear myopathy (ADCNM), a rare disease characterized by skeletal muscle weakness and structural anomalies of the myofibres, including nuclear centralization and mitochondrial mispositioning. Following the clinical report of a Border Collie male with exercise intolerance and histopathological hallmarks of CNM on the muscle biopsy, we identified the c.1393C>T (R465W) mutation in DNM2, corresponding to the most common ADCNM mutation in humans. In order to establish a large animal model for longitudinal and preclinical studies on the muscle disorder, we collected sperm samples from the Border Collie male and generated a dog cohort for subsequent clinical, genetic and histological investigations. Four of the five offspring carried the DNM2 mutation and showed muscle atrophy and a mildly impaired gait. Morphological examinations of transverse muscle sections revealed CNM-typical fibres with centralized nuclei and remodelling of the mitochondrial network. Overall, the DNM2-CNM dog represents a faithful animal model for the human disorder, allows the investigation of ADCNM disease progression, and constitutes a valuable complementary tool to validate innovative therapies established in mice.
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Böhm et al. (2022) studied Autosomal dominant centronuclear myopathy (ADCNM) (n=5). DNM2 c.1393C>T (R465W) mutation was evaluated on Clinical and histological manifestations of CNM. Four of five offspring carrying the DNM2 c.1393C>T mutation showed muscle atrophy, mildly impaired gait, and CNM-typical fibres with centralized nuclei, establishing a faithful dog model for ADCNM.
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