| First Author | Russell C | Year | 1998 |
| Journal | Clin Genet | Volume | 53 |
| Issue | 5 | Pages | 349-61 |
| PubMed ID | 9660052 | Mgi Jnum | J:47999 |
| Mgi Id | MGI:1261404 | Doi | 10.1111/j.1399-0004.1998.tb02745.x |
| Citation | Russell C, et al. (1998) Murine MPS I: insights into the pathogenesis of Hurler syndrome. Clin Genet 53(5):349-61 |
| abstractText | Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease resulting from deficiency of the lysosomal enzyme alpha-L-iduronidase. A murine model which shows complete deficiency in alpha-L-iduronidase activity has been developed and shows phenotypic features similar to severe MPS I in humans. Here we report on the long-term clinical, biochemical, and pathological course of MPS I in mice with emphasis on the skeletal and central nervous system (CNS) manifestations. Affected mice show a progressive clinical course with the development of coarse features, altered growth characteristics and a shortened life span. Progressive lysosomal accumulation is seen in all tissues. Skeletal manifestations represent the earliest clinical finding in MPS I mice with histologic analysis of growth plate and cortical bone revealing evidence that significant early pathology is present. Analysis of the CNS has revealed the novel finding of progressive neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice shows increased levels of GM(2) and GM(3) gangliosides. This murine model clearly shows phenotypic and pathologic features which mimic those seen in severe human MPS I and should be an invaluable tool for the study of the pathogenesis of generalized storage disorders. |
