Pten regulates neuronal soma size: A mouse model of Lhermitte-Duclos disease

Chang Hyuk Kwon, Xiaoyan Zhu, Junyuan Zhang, Lori L. Knoop, Ruby Tharp, Richard J. Smeyne, Charles G. Eberhart, Peter C. Burger, Suzanne J. Baker

Research output: Contribution to journalArticlepeer-review

346 Scopus citations


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 cellautonomous manner and provide new insights into the etiology of Lhermitte-Duclos disease.

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalNature genetics
Issue number4
StatePublished - Dec 2001

ASJC Scopus subject areas

  • Genetics


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