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C07-03 Utrophin in the Golden Retriever muscular dystrophy dog model of duchenne muscular dystrophy.

Howell, J.M., Davies, L. and Lloyd, F. (2006) C07-03 Utrophin in the Golden Retriever muscular dystrophy dog model of duchenne muscular dystrophy. Brain Pathology, 10 (4). pp. 531-536.

Link to Published Version: https://doi.org/10.1111/j.1750-3639.2000.tb00295.x
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Abstract

Duchenne Muscular Dystrophy (DMD)and the animal models mdx mouse and GRMD dog, result from mutations to dystrophin gene. Utrophin is considered to be the autosomal homologue of dystrophin. The ability of high levels of utrophin to rescue dystrophin-deficient muscle has been demonstrated by crossing transgenic mice expressing high levels of utrophin with dystrophin- deficient mdx mice. Upregulating utrophin may provide a therapy for DMD patients. Before the GRMD dog model is used for such an upregulation study it would be helpful to determine the utrophin expression at various ages in these animals. This paper gives the results of staining for utrophin in the muscles of normal, carrier and affected GRMD dogs aged from 13 to 734 days. Consecutive 6m cryostat sections of frozen muscle were placed on sialinated slides and stained by haematoxylin and eosin, Novocastra monoclonal antisera NCL-DPR2 and NCL-DYS 1 for morphology, utrophin and dystrophin respectively. The primary antibody was omitted for technical controls. In normal and carrier pups aged 16 days utrophin staining at the neuromuscular junctions and faintly or partially stained utrophin positive fibres were seen, very few positive fibres were seen at 36 and 63 days of age and were absent at 93 and 94 days. In contrast strong, positive staining for utrophin was seen around the periphery in almost all fibres in muscles of affected GRMD dogs aged from 13 to 734 days. The muscles of all affected GRMD dogs are dystrophin deficient but the clinical signs vary in severity from animal to animal. In this study there was no obvious correlation between severity of clinical signs and degree of utrophin staining. It may be that upregulation of utrophin may lead to a greater amount of utrophin being formed and subsequently an increase in muscle strength or if the upregulation occurs early a diminution in the degree of muscle damage. These possibilities are to be investigated in the GRMD dogs.

Item Type: Journal Article
Publisher: Wiley
URI: http://researchrepository.murdoch.edu.au/id/eprint/62423
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