Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice

Hana N. Dawson*, Adriana Ferreira, Michele V. Eyster, Nupur Ghoshal, Lester I. Binder, Michael P. Vitek

*Corresponding author for this work

Research output: Contribution to journalArticle

328 Scopus citations

Abstract

Conflicting evidence supports a role for tau as an essential neuronal cytoskeletal protein or as a redundant protein whose function can be fulfilled by other microtubule-associated proteins. To investigate the function of tau in axonogenesis, we created tau deficient mice by disrupting the TAU gene. The engineered mice do not express the tau protein, appear physically normal and are able to reproduce. In contrast to a previously reported tau knockout mouse, embryonic hippocampal cultures from tau deficient mice show a significant delay in maturation as measured by axonal and neuritic extensions. The classic technique of selectively enhancing axonal growth by growth on laminin substrates failed to restore normal neuronal maturation of tau knockout neurons. By mating human TAU-gene transgenic and tau knockout mice, we reconstituted tau-deficient neurons with human tau proteins and restored a normal pattern of axonal growth and neuronal maturation. The ability of human tau proteins to rescue tau-deficient mouse neurons confirms that tau expression affects the rate of neurite extension.

Original languageEnglish
Pages (from-to)1179-1187
Number of pages9
JournalJournal of Cell Science
Volume114
Issue number6
StatePublished - 2001

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Keywords

  • Axonogenesis
  • Deficient
  • Knockout
  • Mice
  • Microtubule-associated protein
  • Primary hippocampal culture
  • Tau

ASJC Scopus subject areas

  • Cell Biology

Cite this

Dawson, H. N., Ferreira, A., Eyster, M. V., Ghoshal, N., Binder, L. I., & Vitek, M. P. (2001). Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. Journal of Cell Science, 114(6), 1179-1187.