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

Nat Genet. 2001 Dec;29(4):404-11. doi: 10.1038/ng781.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Cell Cycle Proteins / genetics
  • Cell Division / genetics
  • Cell Size / genetics*
  • Cerebellar Diseases / genetics*
  • Cerebellar Diseases / pathology
  • Cyclin-Dependent Kinase Inhibitor p27
  • Disease Models, Animal
  • Gene Deletion
  • Genes, Tumor Suppressor*
  • Glial Fibrillary Acidic Protein / genetics
  • Immunohistochemistry
  • Integrases / genetics
  • Mice
  • Mice, Transgenic
  • Neurons / pathology*
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / physiology*
  • Phosphorylation
  • Seizures / genetics
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*
  • Viral Proteins / genetics


  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Glial Fibrillary Acidic Protein
  • Tumor Suppressor Proteins
  • Viral Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cre recombinase
  • Integrases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase