MethodsA rat colony with mucopolysaccharidosis VI was established and the clinical, pathological, and biochemical features were characterized. Affected rats had facial dysmorphia, dysostosis multiplex, and increased urinary excretion of glucosaminoglycans (GAGs). Ultrastructural studies revealed storage of GAGs throughout the reticuloendothelial cells, cartilage, and other connective tissues, but no deposition was observed in the nervous system. Biochemical analyses demonstrated that the excreted GAG was dermatan sulfate and the activity of hepatic arylsulfatase B was < 5% of the normal mean value. Pedigree analysis showed that the phenotype was inherited as an autosomal recessive single trait. The availability of a rat model of human mucopolysaccharidosis VI should permit the development and evaluation of various strategies to treat the human disease. (J. Clin. Invest. 1992.91:1099-1104

Congenital aganglionosis rat (AR) is a mutant with an autosomal recessive gene (sl), which shows megacolon caused by the absence of myenteric ganglion cells and white coat-color with a small pigmented spot on the head. Recently, targeted disruption of the endothelin-B (ETB) receptor gene (EDNRB) in the mouse has been reported to cause aganglionic megacolon and coat color spotting resembling the phenotypes of the sl/sl rats. To identify the mutation responsible for the phenotypes of the sl/sl rats, we determined the nucleotide sequences of the EDNRB genes of the sl/sl rats and found that a 301-bp region intervening between direct repeat sequences was deleted in the EDNRB gene, and the deletion produces various transcripts due to aberrant splicing.

No abstract

No abstract

A new rat mutant showing aspermia was investigated. Groups of 4-7 mutant male rats were killed at 3, 5, 10, 15 and 25 weeks of age. Examination by microscope showed apparent abnormalities in the seminiferous epithelium from 3 weeks of age onward. Inclusion-like bodies were observed in the cytoplasm of pachytene spermatocytes from 3 weeks old and instead of spermiation, polynuclear giant cells were formed within the seminiferous epithelium after 5 weeks of age. Histological analysis of seminiferous epithelium of adult mutant rats also showed a marked decrease in the number of preleptotene, leptotene and pachytene spermatocytes and tubules containing only spermatogonia and Sertoli cells in the seminiferous epithelium increased with age. However, the combination of other cellular elements of germ cells in the seminiferous epithelium was similar to that in normal rats and the distribution rate of these seminiferous tubules was close to that of normal rats, indicating that cyclicity of seminiferous epithelium was still maintained in the mutant rats despite the lack of spermiation. Plasma concentrations of FSH and LH were significantly higher in the mutant male rats than in normal male rats at 5 and 10 weeks of age onward, respectively. Plasma concentrations of testosterone were lower in the mutant male rats than in normal male rats. Silastic capsules containing testosterone were implanted into the unilateral testis of adult mutant male rats and animals were autopsied 5 weeks later. However, intratesticular administration of testosterone did not affect restoration of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)