Dystrophic pathology in the intrinsic and extrinsic laryngeal muscles in the mdx mouse.

Abstract

OBJECTIVE: This study aimed to characterize the laryngeal muscles in the mdx mouse model of Duchenne muscular dystrophy (DMD). DESIGN: Pathology was analyzed in the intrinsic and extrinsic laryngeal muscles from mdx mice and compared with other mdx muscle groups and with muscles from age-matched normal control mice. SETTING: In DMD, a dystrophin protein deficiency causes skeletal muscle breakdown. However, some muscle groups, such as the extraocular muscles, are spared from damage. Characterizing other unaffected muscles may form the basis for developing new therapies to alleviate muscle breakdown in DMD. METHODS: Extraocular, diaphragm, tibialis anterior, intrinsic laryngeal, and extrinsic laryngeal muscles were collected from normal (C57Bl/10ScSn) and dystrophic (mdx) mice and analyzed histopathologically. MAIN OUTCOME MEASURES: The extent of pathology was determined by analyzing centrally nucleated muscle fibres, the percentage of necrotic tissue, and uptake of Evan's blue dye into muscle fibres. Expression levels of dystrophin and its related proteins, beta-dystroglycan, utrophin, and caveolin-3, were analyzed by immunofluorescence. RESULTS: The mdx cricothyroid and extrinsic laryngeal muscles had levels of pathology similar to those of the diaphragm and hindlimb muscles, whereas the remaining intrinsic laryngeal muscles showed very mild pathology. Expression of dystrophin, beta-dystroglycan, and utrophin did not differ between mdx muscle groups. Although caveolin-3 was upregulated in all mdx muscles compared with those from normal mice, this upregulation was significantly higher in the mdx extraocular muscles. CONCLUSIONS: With the exception of the cricothyroid, the intrinsic laryngeal muscles may be useful for comparison with the extraocular muscles to identify characteristics that spare them from disease pathology despite a dystrophin deficiency.