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Tau‐4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/ knockout mice
Author(s) -
Sennvik Kristina,
Boekhoorn Karin,
Lasrado Reena,
Terwel Dick,
Verhaeghe Steven,
Korr Hubert,
Schmitz Christoph,
Tomiyama Takami,
Mori Hiroshi,
Krugers Harm,
Joels Marian,
Ramakers Ger J. A.,
Lucassen Paul J.,
Van Leuven Fred
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7735com
Subject(s) - neurite , hippocampal formation , neurogenesis , gene isoform , hippocampus , knockout mouse , genetically modified mouse , biology , microbiology and biotechnology , neuroscience , transgene , phosphorylation , receptor , in vitro , biochemistry , gene
Differential isoform expression and phosphorylation of protein tau are believed to regulate the assembly and stabilization of microtubuli in fetal and adult neurons. To define the functions of tau in the developing and adult brain, we generated transgenic mice expressing the human tau‐4R/2N (htau‐4R) isoform on a murine tau null background, by a knockout/ knockin approach (tau‐KOKI). The main findings in these mice were the significant increases in hippocam‐pal volume and neuronal number, which were sustained throughout adult life and paralleled by improved cognitive functioning. The increase in hippocampal size was found to be due to increased neurogenesis and neuronal survival. Proliferation and neuronal differentiation were further analyzed in primary hippocampal cultures from tau‐KOKI mice, before and after htau‐4R expression onset. In absence of tau, proliferation increased and both neurite and axonal outgrowth were reduced. Htau‐4R expression suppressed proliferation, promoted neuronal differentiation, and restored neu‐rite and axonal outgrowth. We suggest that the tau‐4R isoform essentially contributes to hippocampal development by controlling proliferation and differentiation of neuronal precursors.–Sennvik K., Boekhoorn, K., Lasrado, R., Terwel, D., Verhaeghe, S., Korr, H., Schmitz, C., Tomiyama, T., Mori, H., Krugers, H., Joels, M., Ramakers, G. J. A., Lucassen, P. J., Van Leuven F. Tau‐4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice. FASEB J. 21, 2149–2161 (2007)