Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Jan;136(1):207–217.

A murine model of mucopolysaccharidosis VII. Gross and microscopic findings in beta-glucuronidase-deficient mice.

C Vogler 1, E H Birkenmeier 1, W S Sly 1, B Levy 1, C Pegors 1, J W Kyle 1, W G Beamer 1
PMCID: PMC1877452  PMID: 2105058

Abstract

This report describes the clinical and pathologic alterations found in mice that have a recessively inherited, essentially complete deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span and are dysmorphic and dwarfed. Abnormal gait and decreased joint mobility correlate with glycosaminoglycan accumulation in articular tissue and cartilaginous and bony lesions result in extensive skeletal deformation. In these enzyme-deficient animals, lysosomes, distended by fine fibrillar and granular storage material, are particularly prominent in the macrophage system but also occur in other tissues including the skeletal and central nervous systems. The clinical and pathologic abnormalities in these mutant mice closely parallel those identified in humans with mucopolysaccharidoses (MPS). Therefore, these mice provide a well-defined genetic system for the analysis of the pathophysiology of mucopolysaccharidosis type VII, which has many features in common with the other MPS. The mutant mice provide an attractive animal model to test potential therapies for lysosomal storage disease.

Full text

PDF
207

Images in this article

208Figure 1
on p.208
209Figure 2
on p.209
209Figure 3
on p.209
210Figure 4
on p.210
211Figure 5
on p.211
212Figure 6
on p.212
212Figure 7
on p.212
213Figure 8
on p.213
214Figure 9
on p.214
215Figure 10
on p.215

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernsen P. L., Wevers R. A., Gabreëls F. J., Lamers K. J., Sonnen A. E., Stekhoven J. H. Phenotypic expression in mucopolysaccharidosis VII. J Neurol Neurosurg Psychiatry. 1987 Jun;50(6):699–703. doi: 10.1136/jnnp.50.6.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birkenmeier E. H., Davisson M. T., Beamer W. G., Ganschow R. E., Vogler C. A., Gwynn B., Lyford K. A., Maltais L. M., Wawrzyniak C. J. Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency. J Clin Invest. 1989 Apr;83(4):1258–1266. doi: 10.1172/JCI114010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fischer H. D., Gonzalez-Noriega A., Sly W. S. Beta-glucuronidase binding to human fibroblast membrane receptors. J Biol Chem. 1980 Jun 10;255(11):5069–5074. [PubMed] [Google Scholar]
  4. Frydman M., Steinberger J., Shabtai F., Steinherz R. Interstitial 7q deletion [46,XY,del (7) (pter----cen::q112----qter)] in a retarded quadriplegic boy with normal beta glucuronidase. Am J Med Genet. 1986 Oct;25(2):245–249. doi: 10.1002/ajmg.1320250208. [DOI] [PubMed] [Google Scholar]
  5. Gasper P. W., Thrall M. A., Wenger D. A., Macy D. W., Ham L., Dornsife R. E., McBiles K., Quackenbush S. L., Kesel M. L., Gillette E. L. Correction of feline arylsulphatase B deficiency (mucopolysaccharidosis VI) by bone marrow transplantation. 1984 Nov 29-Dec 5Nature. 312(5993):467–469. doi: 10.1038/312467a0. [DOI] [PubMed] [Google Scholar]
  6. Gehler J., Cantz M., Tolksdorf M., Spranger J., Gilbert E., Drube H. Mucopolysaccharidosis. VII. Beta-glucuronidase deficiency. Humangenetik. 1974 Jul 15;23(2):149–158. doi: 10.1007/BF00282212. [DOI] [PubMed] [Google Scholar]
  7. Gitzelmann R., Wiesmann U. N., Spycher M. A., Herschkowitz N., Giedion A. Unusually mild course of beta-glucuronidase deficiency in two brothers (mucopolysaccharidosis VII). Helv Paediatr Acta. 1978 Nov;33(4-5):413–428. [PubMed] [Google Scholar]
  8. Haskins M. E., Desnick R. J., DiFerrante N., Jezyk P. F., Patterson D. F. Beta-glucuronidase deficiency in a dog: a model of human mucopolysaccharidosis VII. Pediatr Res. 1984 Oct;18(10):980–984. doi: 10.1203/00006450-198410000-00014. [DOI] [PubMed] [Google Scholar]
  9. Hayashi M., Shirahama T., Cohen A. S. Combined cytochemical and electron microscopic demonstration of beta-glucuronidase activity in rat liver with the use of a simultaneous coupling azo dye technique. J Cell Biol. 1968 Feb;36(2):289–297. doi: 10.1083/jcb.36.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoyme H. E., Jones K. L., Higginbottom M. C., O'Brien J. S. Presentation of mucopolysaccharidosis VII (beta-glucuronidase deficiency) in infancy. J Med Genet. 1981 Jun;18(3):237–239. doi: 10.1136/jmg.18.3.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Irani D., Kim H. S., El-Hibri H., Dutton R. V., Beaudet A., Armstrong D. Postmortem observations on beta-glucuronidase deficiency presenting as hydrops fetalis. Ann Neurol. 1983 Oct;14(4):486–490. doi: 10.1002/ana.410140415. [DOI] [PubMed] [Google Scholar]
  12. Krivit W., Pierpont M. E., Ayaz K., Tsai M., Ramsay N. K., Kersey J. H., Weisdorf S., Sibley R., Snover D., McGovern M. M. Bone-marrow transplantation in the Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). Biochemical and clinical status 24 months after transplantation. N Engl J Med. 1984 Dec 20;311(25):1606–1611. doi: 10.1056/NEJM198412203112504. [DOI] [PubMed] [Google Scholar]
  13. Lee J. E., Falk R. E., Ng W. G., Donnell G. N. Beta-glucuronidase deficiency. A heterogeneous mucopolysaccharidosis. Am J Dis Child. 1985 Jan;139(1):57–59. doi: 10.1001/archpedi.1985.02140030059029. [DOI] [PubMed] [Google Scholar]
  14. Nelson A., Peterson L., Frampton B., Sly W. S. Mucopolysaccharidosis VII (beta-glucuronidase deficiency) presenting as nonimmune hydrops fetalis. J Pediatr. 1982 Oct;101(4):574–576. doi: 10.1016/s0022-3476(82)80707-5. [DOI] [PubMed] [Google Scholar]
  15. Peterson L., Parkin J., Nelson A. Mucopolysaccharidosis type VII. A morphologic, cytochemical, and ultrastructural study of the blood and bone marrow. Am J Clin Pathol. 1982 Oct;78(4):544–548. doi: 10.1093/ajcp/78.4.544. [DOI] [PubMed] [Google Scholar]
  16. Sewell A. C., Gehler J., Mittermaier G., Meyer E. Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a report of a new case and a survey of those in the literature. Clin Genet. 1982 Jun;21(6):366–373. doi: 10.1111/j.1399-0004.1982.tb01389.x. [DOI] [PubMed] [Google Scholar]
  17. Shull R. M., Hastings N. E., Selcer R. R., Jones J. B., Smith J. R., Cullen W. C., Constantopoulos G. Bone marrow transplantation in canine mucopolysaccharidosis I. Effects within the central nervous system. J Clin Invest. 1987 Feb;79(2):435–443. doi: 10.1172/JCI112830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sly W. S., Quinton B. A., McAlister W. H., Rimoin D. L. Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J Pediatr. 1973 Feb;82(2):249–257. doi: 10.1016/s0022-3476(73)80162-3. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES