| Abstract: | Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs,
tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained
at the Institute for Animal Experimentation, St. Marianna University Graduate School of
Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its
frequency, we bred the dwarf rats and investigated their characteristics in order to
identify the causative factors of their phenotypes and whether they could be used as a
human disease model. One male and female that produced dwarf progeny were selected, and
reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among
the resultant litter, and dwarfism occurred in both genders, suggesting that it was
inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the
male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In
soft X-ray radiographic and histological examinations, shortening and hypoplasia of the
long bones, such as the tibia and femur, were observed, which were suggestive of
endochondral ossification abnormalities. An immunohistochemical examination detected an
aggrecan synthesis disorder, which might have led to delayed calcification and increased
growth plate thickening in the dwarf rats. We hypothesized that the principal
characteristics of the dwarf rats were systemically induced by insufficient cartilage
calcification in their long bones; thus, we named them cartilage calcification
insufficient (CCI) rats. |
