| Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice. | |
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MedLine Citation:
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PMID: 17341679 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 hippocampal 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 neurite and axonal outgrowth. We suggest that the tau-4R isoform essentially contributes to hippocampal development by controlling proliferation and differentiation of neuronal precursors. |
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Authors:
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Kristina Sennvik; Karin Boekhoorn; Reena Lasrado; Dick Terwel; Steven Verhaeghe; Hubert Korr; Christoph Schmitz; Takami Tomiyama; Hiroshi Mori; Harm Krugers; Marian Joels; Ger J A Ramakers; Paul J Lucassen; Fred Van Leuven |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-06 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 21 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-26 Completed Date: 2007-08-15 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 2149-61 Citation Subset: IM |
Affiliation:
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Experimental Genetics Group, Department Human Genetics, KULeuven-Campus Gasthuisberg ON1-06.602, B-3000 Leuven, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Cell Division Crosses, Genetic Embryo Transfer Embryonic Stem Cells Exploratory Behavior Genetic Vectors Hippocampus / cytology*, growth & development Humans Mice Mice, Inbred C57BL Mice, Knockout Microinjections Neurites / ultrastructure Neurons / cytology* Organ Size Protein Isoforms / genetics, physiology Recognition (Psychology) Recombinant Fusion Proteins / genetics, physiology Stem Cells / cytology Transduction, Genetic tau Proteins / chemistry, genetics, physiology* |
| Chemical | |
Reg. No./Substance:
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0/MAPT protein, human; 0/Protein Isoforms; 0/Recombinant Fusion Proteins; 0/tau Proteins |
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