Major clinical and histopathological characteristics of canine X-linked muscular dystrophy in Japan, CXMDJ.

Canine X-linked muscular dystrophy (CXMD), which was found in a colony of golden retriever, is caused by a mutation in the dystrophin gene and it is a useful model of Duchenne muscular dystrophy (DMD). To investigate the pathogenesis and to develop therapy of DMD, we have established a beagle-based CXMD colony in Japan (CXMDJ) and examined their phenotypes. The mortality by 3 days of age in the third generation (G3) of CXMDJ dogs, 32.3%, was considerably higher than that in normal G3 littermates, 13.3%. Serum creatine kinase (CK) levels of G3 CXMDJ were significantly higher than that of normal male dogs with two peaks: at shortly after birth and around 2 months of age. Diaphragm muscle involvement occurred shortly after birth and was more severe than that of limb muscles. Stress during whelping might be associated with the neonatal death and respiratory muscle involvement. Gait disturbance was also noticed after 2 months of age. The involvement of limb and temporal muscles was observed from 2 months of age, which corresponded with the second peak of serum CK. Macroglossia, dysphagia, drooling and jaw joint contracture were overt from 4 months of age. We noticed severe macroglossia and hypertrophy of the sublingual muscles at the age of 12 months, and these were important features of this model, because dysphagia is one of major symptoms in older DMD patients. Overall, the phenotypes of CXMDJ were roughly identical to those of CXMD dogs in the literature. Beagle-based CXMDJ is smaller and easier to handle than golden retriever, therefore they are a useful model for DMD.