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Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.
- Source :
-
Nature genetics [Nat Genet] 2001 Dec; Vol. 29 (4), pp. 404-11. - Publication Year :
- 2001
-
Abstract
- Somatic inactivation of PTEN occurs in different human tumors including glioblastoma, endometrial carcinoma and prostate carcinoma. Germline mutations in PTEN result in a range of phenotypic abnormalities that occur with variable penetrance, including neurological features such as macrocephaly, seizures, ataxia and Lhermitte-Duclos disease (also described as dysplastic gangliocytoma of the cerebellum). Homozygous deletion of Pten causes embryonic lethality in mice. To investigate function in the brain, we used Cre-loxP technology to selectively inactivate Pten in specific mouse neuronal populations. Loss of Pten resulted in progressive macrocephaly and seizures. Neurons lacking Pten expressed high levels of phosphorylated Akt and showed a progressive increase in soma size without evidence of abnormal proliferation. Cerebellar abnormalities closely resembled the histopathology of human Lhermitte-Duclos disease. These results indicate that Pten regulates neuronal size in vivo in a cell-autonomous manner and provide new insights into the etiology of Lhermitte-Duclos disease.
- Subjects :
- Animals
Brain metabolism
Brain pathology
Cell Cycle Proteins genetics
Cell Division genetics
Cerebellar Diseases pathology
Cyclin-Dependent Kinase Inhibitor p27
Disease Models, Animal
Gene Deletion
Glial Fibrillary Acidic Protein genetics
Immunohistochemistry
Integrases genetics
Mice
Mice, Transgenic
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases genetics
Phosphorylation
Seizures genetics
Tumor Suppressor Proteins genetics
Viral Proteins genetics
Cell Size genetics
Cerebellar Diseases genetics
Genes, Tumor Suppressor
Neurons pathology
Phosphoric Monoester Hydrolases physiology
Tumor Suppressor Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1061-4036
- Volume :
- 29
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 11726927
- Full Text :
- https://doi.org/10.1038/ng781