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A biochemical and ultrastructural evaluation of the type 2 Gaucher mouse


Gaucher mice, created by targeted disruption of the glucocerebrosidase gene, are totally deficient in glucocerebrosidase and have a rapidly deteriorating clinical course analogous to the most severely affected type 2 human patients. An ultrastructural study of tissues from these mice revealed glucocerebroside accumulation in bone marrow, liver, spleen, and brain. This glycolipid had a characteristic elongated tubular structure and was contained in lysosomes, as demonstrated by colocalization with both ingested carbon particles and cathepsin D. In the central nervous system (CNS), glucocerebroside was diffusely stored in microglia cells and in brainstem and spinal cord neurons, but not in neurons of the cerebellum or cerebral cortex. This rostralcaudal pattern of neuronal lipid storage in these Gaucher mice replicates the pattern seen in type 2 human Gaucher patients and clearly demonstrates that glycosphingolipid catabolism and/or accumulation varies within different brain regions. Surprisingly, the cellular pathology of tissue from these Gaucher mice was relatively mild, and suggests that the early and rapid demise of both Gaucher mice and severely affected type 2 human neonates may be the result of both a neurotoxic metabolite, such as glucosylsphingosine, and other factors, such as skin water barrier dysfunction secondary to the absence of glucocerebrosidase activity.

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  1. Adachi M., Wallace B. J., Schneck L., and Volk B. W. (1967) Fine structure of central nervous system in early infantile Gaucher’s disease.Arch. Pathol. 83, 513–526

  2. Armbruster B. L., Carlemalm E., and Chiovetti R. (1982) Specimen preparation for electron microscopy using low temperature embedding resins.J. Microsc. 126, 77–85.

  3. Ballou L. R. (1992) Sphingolipids and cell function.Immunol. Today 13, 339–341.

  4. Banker B. Q., Miller J. O., and Crocker A. C. (1962) The cerebral pathology of infantile Gaucher’s disease, inCerebral Sphingolipidosis (Aronson S. M. and Volk B. W., eds.), pp. 73–99, Academic, New York.

  5. Barranger J. A., and Ginns E. I. (1989) Glucosylceramide lipidosis: Gaucher disease, inThe Metabolic Basis of Inherited Disease II, vol. 6 (Scriver C. R., Beaudet A. L., Sly W. S., and Valle D., eds.), pp. 1677–1698, McGraw-Hill, New York.

  6. Beutler E. and Kuhl W. L. (1970) Detection of defect of Gaucher’s disease and its carrier state in peripheral blood leukocytes.Lancet 1 612–613.

  7. Conradi N. G., Sourander P., Nilsson O., Svennerholm L., and Erikson A. (1984). Neuropathology of the Norrbottnian type of Gaucher disease: morphological and biochemical studies.Acta Neuropathol. (Berl) 65, 99–109.

  8. DeBruyn W. C. and DenBreejen P. (1976) Glycogen, its chemistry and morphological appearance in the electron microscope.Histochem. J. 8, 121–142.

  9. Hannun Y. A. and Bell R. M. (1987) Lysosphingolipids inhibit protein kinase C: implications for the Sphingolipidoses.Science 235, 670–674.

  10. hernandez F. and Bueno M. (1973) Infantile neurological Gaucher’s disease in three siblings: an ultrastructural study.Virchows Arch. (Pathol. Anat.) 360, 27–32.

  11. Holleran W. M., Ginns E. I., Menon G. K., Grundmann J. U., Fartasch M., McKinney C. E., Elias P. M., and Sidransky E. (1994) Consequences of β-glucocerebrosidase deficiency in epidermis: ultrastructure and permeability barrier alterations in Gaucher disease.J. Clin. Invest. 93, 1756–1764.

  12. Holleran W. M., Menon G. K., Elias P. M., Ginns E. I., and Sidransky E. (1983a) β-glucocerebrosidase-deficient transgenic mice have abnormal stratum corneum lamellar bilayers.Clin. Res. 41(2), 402A.

  13. Holleran W. M., Takagi Y., Menon G. K., Legler G., Feingold K. R., and Elias P. M. (1993b) Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.J. Clin. Invest. 91, 1656–1664.

  14. Kaye E. M., Ullman M. D., Wilson E. R., and Barranger J. A. (1986) Type 2 and type 3 Gaucher disease: a morphological and biochemical study.Ann. Neurol. 20 223–230.

  15. Kundu S. K. (1981) inMethods of Enzymology Lowenstein J. M., ed.), pp. 185–204, Academic, New York.

  16. Lee R. E. (1982) The pathology of Gaucher disease, inGaucher’s Disease: A Century of Delineation and Research (Desnick R. J., Gatt S., and Grabowski G. A., eds.), pp. 177–218, Liss, New York.

  17. Lee, R. E., Worthington C. R., and Glew R. H. (1973) The bilayer nature of deposits occurring in Gaucher’s disease.Arch. Biochem. Biophys. 159, 259–266.

  18. Martin B. M., Sidransky E., and Ginns E. I. (1989) Gaucher disease: advances and challenges.Adv. Pediatr. 36, 277–306.

  19. Nilsson O. and Svennerholm L. (1982) Accumulation of glucosylceramide and glucosylsphingosine in cerebrum and cerebellum in infantile and juvenile Gaucher disease.J. Neurochem. 39, 709–718.

  20. Sidransky E., Sherer D. M., and Ginns E. I. (1992) Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene.Pediatric Res. 32, 494–498.

  21. Svennerholm L., Hakansson G., Mansson J. E., and Nilsson O. (1982) Chemical differentiation of the Gaucher subtypes, inGaucher’s Disease: A Century of Delineation and Research (Desnick R. J., Gatt S., and Grabowski G. A., eds.), pp. 231–252, Liss, New York.

  22. Tybulewicz, V. L. J., Tremblay M. L., LaMarca M. E., Willemsen R., Stubblefield B. K., Winfield S., Zablocka B., Sidransky E., Martin B. M., Huang, S. P., Mintzer K. A., Westphal H., Mulligan R. C., and Ginns E. I. (1992) Animal model of Gaucher’s disease from targeted disruption of the mouse glucocerebrosidase gene.Nature 357, 407–410.

  23. Willemsen R., VanDongen J., Aerts J. M. F. G., et al. (1988) An immunoelectron microscopic study of glucocerebrosidase in type 1 Gaucher’s disease spleen.Ultrastruct. Pathol. 12, 471–478.

  24. Zeller C. B. and Marchase R. B. (1992) Gangliosides as modulators of cell function.Am. J. Physiol. 262, C1341-C1355.

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Correspondence to E. I. Ginns.

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Willemsen, R., Tybulewicz, V., Sidransky, E. et al. A biochemical and ultrastructural evaluation of the type 2 Gaucher mouse. Molecular and Chemical Neuropathology 24, 179 (1995).

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Index Entries

  • Type 2 Gaucher mice
  • targeted disruption
  • glucocerebrosidase
  • glucocerebroside
  • lysosomes
  • microglia
  • neurons