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. 1978 Sep;92(3):755–769.

Turnover of kidney beta-glucuronidase in normal and Chédiak-Higashi (beige) mice.

R T Swank, E J Brandt
PMCID: PMC2018270  PMID: 686157

Abstract

Kidney beta-glucuronidase turnover has been examined by specific antibody methods in normal C57BL/6J mice and in coisogenic C57BL/6J beige mice, an animal model for the human Chédiak-Higashi syndrome. No effect of the beige gene on the rate of glucuronidase synthesis was detected in either untreated or testosterone-treated mice. Moreover, glucuronidase of beige mice decayed relatively slowly in pulse labeling and in hormone withdrawal experiments. Direct measurements of secretion confirmed that both in the presence of testosterone and following its withdrawal, there was a threefold lower rate of secretion of kidney glucuronidase in beige mice. Following hormone withdrawal, the loss of glucuronidase activity in beige mice was biphasic, with the second more slowly turning over component apparently lost by a nonsecretory mechanism. This persistent nonsecreted glucuronidase activity was specifically associated with giant lysosomes in kidney proximal tubule cells near the corticomedullary border. Thus, there are two major populations of lysosomes in proximal tubule cells of beige mice. Cells of the outer cortex contain mainly morphologically normal lysosomes, and their lysosomal enzymes are secreted at near normal rates. However, lysosomal enzymes derived from the giant lysosomes of cells near the corticomedullary border are secreted either very slowly or not at all. The altered secretion of lysosomal enzymes from specific kidney cells of beige mice may serve as a model system for study of defective fusion of lysosomes with phagocytosed bacteria in cells of Chédiak-Higashi patients.

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Selected References

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  1. Blume R. S., Wolff S. M. The Chediak-Higashi syndrome: studies in four patients and a review of the literature. Medicine (Baltimore) 1972 Jul;51(4):247–280. [PubMed] [Google Scholar]
  2. Boxer G. J., Holmsen H., Robkin L., Bang N. U., Boxer L. A., Baehner R. L. Abnormal platelet function in Chediak-Higashi syndrome. Br J Haematol. 1977 Apr;35(4):521–533. doi: 10.1111/j.1365-2141.1977.tb00618.x. [DOI] [PubMed] [Google Scholar]
  3. Boxer L. A., Watanabe A. M., Rister M., Besch H. R., Jr, Allen J., Baehner R. L. Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. N Engl J Med. 1976 Nov 4;295(19):1041–1045. doi: 10.1056/NEJM197611042951904. [DOI] [PubMed] [Google Scholar]
  4. Brandt E. J., Elliott R. W., Swank R. T. Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi (beige) mice. J Cell Biol. 1975 Dec;67(3):774–788. doi: 10.1083/jcb.67.3.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brandt E. J., Swank R. T. The Chediak-Higashi (beige) mutation in two mouse strains. Allelism and similarity in lysosomal dysfunction. Am J Pathol. 1976 Mar;82(3):573–588. [PMC free article] [PubMed] [Google Scholar]
  6. Buchanan G. R., Handin R. I. Platelet function in the Chediak-Higashi syndrome. Blood. 1976 Jun;47(6):941–948. [PubMed] [Google Scholar]
  7. Bullock L. P., Bardin C. W., Ohno S. The androgen insensitive mouse: absence of intranuclear androgen retention in the kidney. Biochem Biophys Res Commun. 1971 Sep 17;44(6):1537–1543. doi: 10.1016/s0006-291x(71)80261-9. [DOI] [PubMed] [Google Scholar]
  8. Davis W. C., Spicer S. S., Greene W. B., Padgett G. A. Ultrastructure of bone marrow granulocytes in normal mink and mink with the homolog of the Chediak-Higashi trait of humans. I. Origin of the abnormal granules present in the neutrophils of mink with the C-HS trait. Lab Invest. 1971 Apr;24(4):303–317. [PubMed] [Google Scholar]
  9. Essner E., Oliver C. A hereditary alteration in kidneys of mice with Chediak-Higashi syndrome. Am J Pathol. 1973 Oct;73(1):217–232. [PMC free article] [PubMed] [Google Scholar]
  10. Essner E., Oliver C., Haimes H. Fate of exogenous peroxidase in renal lysosomes of mice with Chediak-Higashi syndrome. Am J Pathol. 1974 Dec;77(3):407–422. [PMC free article] [PubMed] [Google Scholar]
  11. Essner E., Oliver C. Lysosome formation in hepatocytes of mice with Chèdiak-Higashi syndrome. Lab Invest. 1974 May;30(5):597–607. [PubMed] [Google Scholar]
  12. Gallin J. I., Klimerman J. A., Padgett G. A., Wolff S. M. Defective mononuclear leukocyte chemotaxis in the Chediak-Higashi syndrome of humans, mink, and cattle. Blood. 1975 Jun;45(6):863–870. [PubMed] [Google Scholar]
  13. Kimball H. R., Ford G. H., Wolff S. M. Lysosomal enzymes in normal and Chediak-Higashi blood leukocytes. J Lab Clin Med. 1975 Oct;86(4):616–630. [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Meisler M. H. Synthesis and secretion of kidney beta-galactosidase in mutant le/le mice. J Biol Chem. 1978 May 10;253(9):3129–3134. [PubMed] [Google Scholar]
  16. Oliver J. M. Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome. Am J Pathol. 1976 Nov;85(2):395–418. [PMC free article] [PubMed] [Google Scholar]
  17. Root R. K., Rosenthal A. S., Balestra D. J. Abnormal bactericidal, metabolic, and lysosomal functions of Chediak-Higashi Syndrome leukocytes. J Clin Invest. 1972 Mar;51(3):649–665. doi: 10.1172/JCI106854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tominco S., Paigen K. Egasyn, a protein complexed with microsomal beta-glucuronidase. J Biol Chem. 1975 Feb 10;250(3):1146–1148. [PubMed] [Google Scholar]
  19. Wang C-C, Touster O. Turnover studies on proteins of rat liver lysosomes. J Biol Chem. 1975 Jul 10;250(13):4896–4902. [PubMed] [Google Scholar]
  20. Warburton M. J., Wynn C. H. The turnover of hamster fibroblast lysosomal beta-D-glucuronidase. Biochem J. 1977 Jan 15;162(1):201–203. doi: 10.1042/bj1620201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Windhorst D. B., Padgett G. The Chediak-Higashi syndrome and the homologous trait in animals. J Invest Dermatol. 1973 Jun;60(6):529–537. doi: 10.1111/1523-1747.ep12703609. [DOI] [PubMed] [Google Scholar]

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