Loss of the tuberous sclerosis complex protein tuberin causes Purkinje cell degeneration.

ABSTRACT: Tuberous sclerosis complex (TSC) is a neurogenetic disorder that often causes brain abnormalities leading to epilepsy, developmental delay, and autism. TSC is caused by inactivating mutations in either of the genes encoding the proteins hamartin (TSC1) and tuberin (TSC2). These proteins form a heterodimer that inhibits the mammalian target of rapamycin complex 1 (mTORC1) pathway, controlling translation and cell growth. Loss of either protein results in dysregulated mTORC1 activation, an important aspect of TSC pathogenesis. About thirty percent of TSC patients have cerebellar pathology that is poorly understood. To investigate the effects of TSC on the cerebellum, we created a mouse model in which the Tsc2 gene was selectively deleted from Purkinje cells starting at postnatal day 6 (P6).

SUBMITTER: Reith RM 

PROVIDER: S-EPMC3096682 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature