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- Title
Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.
- Authors
Kwon, Chang-Hyuk; Zhu, Xiaoyan; Zhang, Junyuan; Knoop, Lori L.; Tharp, Ruby; Smeyne, Richard J.; Eberhart, Charles G.; Burger, Peter C.; Baker, Suzanne J.
- 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-loxPtechnology 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 cellautonomous manner and provide new insights into the etiology of Lhermitte-Duclos disease.
- Subjects
TUMOR suppressor genes; LABORATORY mice
- Publication
Nature Genetics, 2001, Vol 29, Issue 4, p404
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng781