Cell-cycle markers in a transgenic mouse model of human tauopathy

Increased levels of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1

Patrice Delobel, Isabelle Lavenir, Bernardino Ghetti, Max Holzer, Michel Goedert

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Recent evidence has suggested that an abnormal reactivation of the cell cycle may precede and cause the hyperphosphorylation and filament formation of tau protein in Alzheimer's disease and other tauopathies. Here we have analyzed the expression and/or activation of proteins involved in cell-cycle progression in the brain and spinal cord of mice transgenic for mutant human P301S tau protein. This mouse line recapitulates the essential molecular and cellular features of the human tauopathies, including hyperphosphorylation and filament formation of tau protein. None of the activators and co-activators of the cell cycle tested were overexpressed or activated in 5-month-old transgenic mice when compared to controls. By contrast, the levels of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were increased in brain and spinal cord of transgenic mice. Both inhibitors accumulated in the cytoplasm of nerve cells, the majority of which contained inclusions made of hyperphosphorylated tau protein. A similar staining pattern for p21Cip1 and p27Kip1 was also present in the frontal cortex from a case of FTDP-17 with the P301L tau mutation. Thus, reactivation of the cell cycle was not involved in tau hyperphosphorylation and filament formation, consistent with expression of p21Cip1 and p27Kip1 in tangle-bearing nerve cells.

Original languageEnglish
Pages (from-to)878-887
Number of pages10
JournalAmerican Journal of Pathology
Volume168
Issue number3
DOIs
StatePublished - Mar 2006

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Tauopathies
Cyclin-Dependent Kinases
tau Proteins
Transgenic Mice
Cell Cycle
Spinal Cord
Neurons
Frontotemporal Dementia
Brain
Frontal Lobe
Alzheimer Disease
Cytoplasm
Staining and Labeling
Mutation
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cell-cycle markers in a transgenic mouse model of human tauopathy : Increased levels of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1. / Delobel, Patrice; Lavenir, Isabelle; Ghetti, Bernardino; Holzer, Max; Goedert, Michel.

In: American Journal of Pathology, Vol. 168, No. 3, 03.2006, p. 878-887.

Research output: Contribution to journalArticle

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