The study of sonic hedgehog signaling pathway in the development of lysosomal acid phosphatase (Acp2) mutant mice cerebellar granule cells
A lysosomal acid phosphatase 2 (Acp2) mutant mouse (naked-ataxia, nax) shows severe cerebellar cortex defect with a significant reduction in granule cells in the cerebellum. The sonic hedgehog (SHH) and N-Myc pathways are important for granule cell precursor proliferation and differentiation. The project tests the hypothesis that the proliferation defect of granule cells is associated with SHH - N-Myc pathway impairment in the nax mutant cerebellum. To investigate morphological changes in the nax cerebellum and alteration in the SHH - N-Myc pathway, in vivo and in vitro immunohistochemistry and Western blotting were used. My data showed a strikingly reduced N-Myc expression in the nax cerebellum, which was accompanied by an increase in proteasome activity, suggesting that the significant reduction of granule cells in nax cerebellum is potentially due to the dysregulation of N-Myc via the abnormal ubiquitin-proteasome system activity.