Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease.

摘要: Initially identified in high-grade gliomas, mutations the PTEN tumor-suppressor are also found many sporadic cancers and a few related autosomal dominant hamartoma syndromes. is 3'-specific phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) phosphatase functions as negative regulator of PI3K signaling. We generated tissue-specific deletion mouse homolog Pten to address its role brain function. Mice homozygous for this (PtenloxP/loxP;Gfap-cre), developed seizures ataxia by 9 wk died 29 wk. Histological analysis showed enlargement PtenloxP/loxP;Gfap-cre mice consequence primary granule-cell dysplasia cerebellum dentate gyrus. mutant cells cell-autonomous increase soma size elevated phosphorylation Akt. These data represent first evidence Akt cell regulation mammals provide an animal model human phakomatosis condition, Lhermitte-Duclos disease (LDD).