Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation. (28th October 2021)

• Record Type: Journal Article
• Authors: Kato, Takashi; Igarashi, Atsushi; Sesaki, Hiromi; Iijima, Miho
• Is Part Of: Genes to cells. Volume 26:Number 12(2021)
• Page Start: 1014
• Page End: 1022
• Publication Date: 2021-10-28
• Subjects: brain -- mouse -- neuron -- nuclear PTEN -- PTEN; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12902
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: 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. Abstract : The current study generated a new mouse line that shows a strong decrease in the localization of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the nucleus without affecting the protein stability, phosphatase activity, and phosphorylation in the C‐terminal tail region. The nuclear PTEN‐deficient mice produce smaller neurons and develop microcephaly. Therefore, this mouse line provides a useful animal model to study the role of PTEN in the nucleus in vivo.