Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
1 Department of Children’s Dentistry, Stony Brook University, Stony Brook, NY, 11894-8701, USA
2 Health Science Center, Stony Brook University, Stony Brook, NY, 11794-8701, USA
3 Department of Dentistry, University of Rochester School of Medicine & Dentistry, Rochester, NY, 14642, USA
4 Neurobiology & Anatomy, University of Rochester School of Medicine & Dentistry, Rochester, NY, 14642, USA
Journal of Neuroinflammation 2012, 9:186 doi:10.1186/1742-2094-9-186Published: 4 August 2012
This study evaluated whether GM2 ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing β-hexosaminidase rescue experiments in neurons of HexB−/− mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of HexB−/− mice by the Thy1 promoter. Despite β-hexosaminidase restoration in neurons was sufficient in rescuing HexB−/− mice from GM2 neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM2 presence in this cell type. In conclusion, our results suggest that neuroinflammation is not sufficient to elicit neurodegeneration as long as neuronal function is restored.