Abstract:The purpose of this study was to develop a strain of canine X-linked muscular dystrophy (CXMD), a model of Duchenne muscular dystrophy, in Japan. A female beagle was artificially inseminated with frozen-thawed spermatozoa derived from an affected golden retriever. Subsequently, two carrier female dogs (G1 carriers) and four normal male littermates were produced. Thereafter, the two G1 carriers were mated with beagle sires. As a result, each bitch whelped three times, and out of 54 pups, 17 affected male descendants, and 11 carrier female descendants (G2 carriers) were detected. One G2 carrier was then mated with a beagle sire and 15 pups in two whelpings were produced, including five affected males and four carrier females (G3 carriers). A total of 10 female beagles were artificially inseminated to evaluate the fertility of the frozen-thawed spermatozoa from the two affected dogs. The whelping rates of the two affected dogs were 4/5 and the litter sizes were 5.0 ± 1.41 and 6.0 ± 0.82, respectively. These results indicate that a canine X-linked muscular dystrophy colony has been established in Japan. We called them CXMD J .

Background: Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD) has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMD J ) and examined the cardiac involvement.

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-This study comprehensively describes the effects of various levels of food reduction on a wide range of toxicological parameters in dietary-optimized rats (fed with approximately 75% of ad libitum food consumption daily; 16 g and 22 g/day for females and males, respectively) that has been established as a nutritionally appropriate and well-controlled animal model in conducting toxicity studies. Toxicological parameters, including general condition, ophthalmology, clinical pathology and anatomic pathology, were examined in dietary-optimized Crl:CD(SD) female and male rats fed 16 g and 22 g/day (control), 12 g and 17 g/day (75% group), 8 g and 11 g/day (50% group), or 4 g and 6 g/day (25% group), respectively for 2 weeks. There was mortality and morbidity including reddish urine in 25% -cular hemolysis induced by severe food reduction. Hemoconcentration, decreased leukocytes and platelets, decreases in nutritional elements (serum glucose, protein, and lipids), increased aspartate aminotransferase and alanine aminotransferase, imbalanced electrolytes, and/or decreased urinary pH were observed in all restriction groups. Histopathologically remarkable changes included erythrophagocytosis in the spleen/liver and renal tubular necrosis with hyaline cast/droplets in 25% group; in addition to bone marrow depletion, lymphoid depletion in thymus/spleen/lymph node, and/or decreased secretion in the prostate/seminal vesicle in all restriction groups. Most of these changes were considered attributable to nutrifood reduction. These results will enable toxicologists to help distinguish primary drug-induced effects from secondary changes associated with decreases in food consumption.

The present study demonstrated that NOS inhibitors prevented the development of cataracts in selenite-treated rats. The results also suggest that nitric oxide had an important role in the development of selenite-induced cataracts.