Abstract
Hurler syndrome (MPS IH) is caused by a mutation in the gene encoding alpha-L-iduronidase (IDUA) and leads to the accumulation of partially degraded glycosaminoglycans (GAGs). Ganglioside content is known to increase secondary to GAG accumulation. Most studies in organisms with MPS IH have focused on changes in gangliosides GM3 and GM2, without the study of other lipids. We evaluated the total lipid distribution in the whole brain and cerebellum of MPS IH (Idua -/-?) and control (Idua +/?) mice at 6 months and at 12 months of age. The content of total sialic acid and levels of gangliosides GM3, GM2, and GD3 were greater in the whole brains of Idua -/-? mice then in Idua +/? mice at 12 months of age. No other significant lipid differences were found in either whole brain or in cerebellum at either age. The accumulation of ganglioside GD3 suggests that neurodegeneration occurs in the Idua -/-? mouse brain, but not to the extent seen in human MPS IH brain.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1669-1676 |
| Number of pages | 8 |
| Journal | Neurochemical Research |
| Volume | 36 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2011 |
Bibliographical note
Funding Information:Acknowledgments This work has been funded in part by the Minnesota Medical Foundation, Children’s Cancer Research Fund, MN (JT), NIH grant NS055195 and Boston College Research Expense Fund (TNS).
Keywords
- GD3
- Gangliosides
- Hurler syndrome
- Lipids
- MPS IH
- Mouse model