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Pigmentation and lysosome function in mice homozygous for both pale ear and Beige-J pigment genes

Published online by Cambridge University Press:  14 April 2009

Edward K. Novak ,
Richard T. Swank  and
Miriam H. Meisler
Edward K. Novak
Affiliation:
Department of Molecular Biology, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, N.Y. 14263
Richard T. Swank
Affiliation:
Department of Molecular Biology, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, N.Y. 14263
Miriam H. Meisler
Affiliation:
Department of Human Genetics, The University of Michigan, 1137 East Catherine Street, Ann Arbor, Michigan 48109
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We have examined mice doubly homozygous for both pale ear (ep/ep) and beige (bgJ/bgJ) mutations in order to detect genetic interactions between these 2 loci affecting pigmentation and lysosome physiology. The doubly homozygous mouse has a new pigmentation phenotype consistent with independent effects of ep and bg. The beige (Brandt, Elliott & Swank, 1975) and pale ear (Novak & Swank, 1979)genes have abnormal kidney lysosomal enzyme accumulation caused by defective secretion into urine. No cumulative effect on these functions was observed in the new double mutant phenotype. The new phenotype has giant lysosomes typical of the beige mutation. Unexpectedly, the beige gene corrects the effect of the pale ear on serum lysosomal enzyme concentration. There is also a gene dosage effect of the beige gene on this serum lysosomal enzyme phenotype. The results suggest that the beige and pale ear genes affect the same pathway(s) of lysosome biosynthesis and/or processing. The action of the beige gene may precede that of the pale ear gene in lysosome physiology.

Type
Research Article
Information
Genetics Research , Volume 35 , Issue 2 , April 1980 , pp. 195 - 204
Copyright
Copyright © Cambridge University Press 1980

References

REFERENCES

Boxer, G. J., Holmsen, H., Robbin, L., Bang, N. U., Boxer, L. A. & Baehner, R. L. (1977). Abnormal platelet function in Chediak–Higashi syndrome. British Journal of Haematology 35, 521–533.CrossRefGoogle ScholarPubMed
Boxer, L. A., Watanabe, A. M., Rister, M., Besch, H., Allen, J. & Baehner, B. L. (1976). Correction of leukocyte function in Chediak–Higashi syndrome by ascorbate. New England Journal of Medicine 295, 1041–1045.CrossRefGoogle ScholarPubMed
Brandt, E. J., Elliott, R. W. & Swank, R. T. (1975). Defective lysosomal enzyme secretion in kidneys of Chediak–Higashi (beige) mice. Journal of Cell Biology 67, 774–788.Google Scholar
Brandt, E. J., Swank, R. T., Novak, E. K. & Skudlarek, M. (1978). The murine Chediak–Higashi mutation: a review. In Animal Models of Comparative and Developmental Aspects of Immunity and Disease (ed. Gershwin, M. E. and Cooper, E. L.), pp. 223–235. New York: Pergamon Press.Google Scholar
Chi, E. Y. & Lagunoff, D. (1975). Abnormal mast cell granules in the beige (Chediak–Higashi Syndrome) mouse. Journal of Histochemistry and Cytochemistry 23, 117–122.CrossRefGoogle ScholarPubMed
Davis, W., Spicer, S., Green, W. & Padgett, G. (1971). Ultrastructure of bone marrow and peripheral blood of normal mink and mink with the homologue of the Chediak–Higashi trait in humans. II. Cytoplasmic granules in eosinophils, basophils, mononuclear cells and platelets. American Journai of Pathology 63, 411–431.Google Scholar
Frankel, F. R., Tucker, R. W., Bruce, J. & Stenberg, R. (1978). Fibroblasts and macrophages of mice with the Chediak–Higashi syndrome have microtubules and actin cables. Journal of Cell biology 79, 401–408.Google Scholar
Gallin, J. I., Elin, R. J., Hubert, R. T., Fauci, A. S., Kaliner, M. A. & Wolf, S. M. (1979). Efficacy of ascorbic acid in Chediak–Higashi syndrome (CHS): studies in humans and mice. Blood 53, 226–234.CrossRefGoogle ScholarPubMed
Haak, R. A., Ingraham, L. M., Baehner, R. L. & Boxer, L. A. (1979). Membrane fluidity in human and mouse Chediak–Higashi leukocytes. Journal of Clinical Investigation 64, 138–144.Google Scholar
Hayashi, M. (1964). Distribution of β-glucuronidase in rat tissues employing the naphthol AS-Bl glucuronide hexazonium pararosanilin method. Journal of Histochemistry and Cytochemistry 12, 659–669.Google Scholar
Hinds, K. & Danes, B. S. (1976). Microtubular defect in Chediak–Higashi Syndrome. Lancet ii, 146–147.Google Scholar
Holland, J. M. (1976). Serotonin deficiency and prolonged breeding in Beige mice. Proceedings of the Society for Experimental Biology and Medicine 151, 32–39.CrossRefGoogle Scholar
Lane, P. W. & Green, E. L. (1967). Pale ear and light ear in the house mouse. Journal of Heredity 58, 17–20.Google Scholar
McCluer, R. H., Gross, S. K., Sapirstein, V. S. & Meisler, M. H. (1979). Testosterone effects on kidney and urinary glycolipids in the light-eared mouse mutant. Federation Proceedings 38, 932a.Google Scholar
Meisler, M. (1978). Synthesis and secretion of kidney β-galactosidase in mutant le/le mice. Journal of Biological Chemistry 253, 3129–3134.CrossRefGoogle ScholarPubMed
Novak, E. K. & Swank, R. T. (1979). Lysosomal dysfunctions associated with mutations at mouse pigment genes. Genetics 92, 189–204.CrossRefGoogle ScholarPubMed
Oliver, J. M. (1976). Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak–Higashi Syndrome. American Journal of Pathology 85, 395–412.Google ScholarPubMed
Oliver, C. & Essner, E. (1973). Distribution of anomolous lysosomes in the beige mouse: a homologue of Chediak–Higashi Syndrome. Journal of Histochemistry and Cytochemistry 21, 218–228.CrossRefGoogle Scholar
Paigen, K. (1971). The genetics of enzyme realization. In Enzyme Synthesis and Degradation in Mammalian Systems (ed. Rechcigl, M.). Basel: Karger.Google Scholar
Silvers, W. K. (1979). The Coat Colors of Mice, p. 141. New York: Springer-Verlag.Google Scholar
Smith, K. & Ganschow, R. E. (1978). Turnover of murine β-glucuronidase, comparison among liver, kidney and spleen and between lysosomes and microsomes. Journal of Biological Chemistry 253, 5437–5442.CrossRefGoogle ScholarPubMed
Swank, R. T. & Brandt, E. J. (1978). Turnover of kidney β-glucuronidase in normal and Chediak–Higashi (beige) mice. American Journal of Pathology. 92, 755–772.Google Scholar
Swank, R. T., Novak, E., Brandt, E. J. & Skudlarek, M. (1978). Genetics of lysosomal functions. In Protein Turnover and Lysosomal Function, (ed. Doyle, D. and Segal, H.). New York: Academic Press.Google Scholar
Tomino, S. & Meisler, M. (1975). Biochemical and immunological studies of purified mouse β-galactosidase. Journal of Biological Chemistry 250, 7752–7758.CrossRefGoogle ScholarPubMed
Wang, C. & Touster, O. (1975). Turnover studies on proteins of rat liver lysosomes. Journal of Biological Chemistry 250, 4896–4902.CrossRefGoogle Scholar
Windhorst, D. B., White, J. G., Zelickson, A. S., Clawson, C. C., Dent, P. B., Pollara, B. & Good, R. A. (1968). The Chediak–Higashi anomaly and the aleution trait in mink: homologous defects of lysosome structure. Annals of the New York Academy of Sciences 155, 818–846.Google Scholar