Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation

Genes Cells. 2021 Dec;26(12):1014-1022. doi: 10.1111/gtc.12902. Epub 2021 Oct 28.


Many human diseases, including cancer and neurological abnormalities, are linked to deficiencies of phosphatase and tensin homolog deleted on chromosome ten (PTEN), a dual phosphatase that dephosphorylates both lipids and proteins. PTEN functions in multiple intracellular locations, including the plasma membrane and nucleus. Therefore, a critical challenge to understand the pathogenesis of PTEN-associated diseases is to determine the specific role of PTEN at different locations. Toward this goal, the current study generated a mouse line in which lysine 13, which is critical for the nuclear localization of PTEN, is changed to arginine in the lipid-binding domain using the CRISPR-Ca9 gene-editing system. We found that PTENK13R mice show a strong decrease in the localization of PTEN in the nucleus without affecting the protein stability, phosphatase activity, and phosphorylation in the C-terminal tail region. PTENK13R mice are viable but produce smaller neurons and develop microcephaly. These data demonstrate that PTENK13R mice provide a useful animal model to study the role of PTEN in the nucleus in vivo.

Keywords: PTEN; brain; mouse; neuron; nuclear PTEN.

MeSH terms

  • Animals
  • Cell Nucleus* / metabolism
  • Disease Models, Animal
  • Mice
  • Mutation
  • Neurons / metabolism
  • PTEN Phosphohydrolase* / genetics
  • PTEN Phosphohydrolase* / metabolism
  • Phosphorylation


  • PTEN Phosphohydrolase