Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation

Abstract

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. © 2012 Kyrkanides et al.; licensee BioMed Central Ltd.