title: The Chediak-Higashi (beige) mutation in two mouse strains. Allelism and similarity in lysosomal dysfunction.
abstract: A mutation called beige, with a phenotype similar to that of the human Chediak-Higashi syndrome, has occurred independently in two inbred strains of mice. Beige-J (bgj) occurred as a spontaneous mutation in the C57B1/6J strain and beige (bg) was radiation-induced in mice of heterogenous background which were then inbred as strain SB/Le (bg/bg), the subject of the present study. As in the previously characterized C57Bl/6J beige-J mutant, there is a correlation between abnormal lysosome structure and defective lysosome function in SB/Le beige mice. They secrete much less than normal amounts of lysosomal enzymes from proximal tubule cells and, hence, have increased lysosomal enzyme activity in kidney. In addition, after treatment of either beige strain with androgen, numerous giant beta-glucuronidase-containing lysosomes are present in kidney proximal tubule cells near the corticomedullary border. By directly measuring the rate of beta-glucuronidase synthesis in androgen-treated SB/Le beige mouse kidney, it was shown that the greater accumulation of this lysosomal enzyme in proximal tubule cells was not due to an increase in its rate of synthesis. Genetic analysis of the beige mutations in the two mutant strains demonstrated that both mutant genes are recessive and, in fact, are allelic. The results suggest that both beige strains are defective in intracellular motility of lysosomes and/or their fusion with cellular membranes, and that both mutant strains are suitable experimental models for the human Chediak-Higashi syndrome.
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002609:Chediak-Higashi Syndrome / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D004195:Disease Models, Animal; D005260:Female; D005696:Galactosidases / Q000378:metabolism; D005808:Genes, Recessive; D005966:Glucuronidase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D010641:Phenotype
chemical_list: D005696:Galactosidases; D005966:Glucuronidase; D000118:Acetylglucosaminidase