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Bone Marrow Transplant. 2012 Sep;47(9):1235-40. doi: 10.1038/bmt.2011.239. Epub 2011 Dec 19.

Increased longevity and metabolic correction following syngeneic BMT in a murine model of mucopolysaccharidosis type I.

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Gene Therapy Program, Institute of Human Genetics, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.


Mucopolysaccharidosis type I (MPS I) is an autosomal recessive inherited disease caused by deficiency of the glycosidase α-L-iduronidase (IDUA). Deficiency of IDUA leads to lysosomal accumulation of glycosaminoglycans (GAG) heparan and dermatan sulfate and associated multi-systemic disease, the most severe form of which is known as Hurler syndrome. Since 1981, the treatment of Hurler patients has often included allogeneic BMT from a matched donor. However, mouse models of the disease were not developed until 1997. To further characterize the MPS-I mouse model and to study the effectiveness of BMT in these animals, we engrafted a cohort (n=33) of 4-8-week-old Idua(-/-) animals with high levels (88.4±10.3%) of wild-type donor marrow. Engrafted animals displayed an increased lifespan, preserved cardiac function, partially restored IDUA activity in peripheral organs and decreased GAG accumulation in both peripheral organs and in the brain. However, levels of GAG and GM3 ganglioside in the brain remained elevated in comparison to unaffected animals. As these results are similar to those observed in Hurler patients following BMT, this murine-transplantation model can be used to evaluate the effects of novel, more effective methods of delivering IDUA to the brain as an adjunct to BMT.

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