Flexible Accelerated STOP Tetracycline Operator-Knockin (FAST): A Versatile and Efficient New Gene Modulating System

Kenji F. Tanaka, Susanne E. Ahmari, E. David Leonardo, Jesse W. Richardson-Jones, Elaine C. Budreck, Peter Scheiffele, Shouta Sugio, Naoko Inamura, Kazuhiro Ikenaka, René Hen

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Abstract

We created the Flexible Accelerated STOP Tetracycline Operator (tetO)-knockin (FAST) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. A single gene targeting event yields two distinct knockin mice-STOP-tetO and tetO knockin-that permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue, 3) tetracycline-controlled transcriptional activator (tTA)-mediated misexpression, 4) tetracycline-controlled transcriptional activator (tTA)-mediated overexpression, and 5) tetracycline-controlled transcriptional silencer (tTS)-mediated conditional knockout/knockdown. Using the FAST system, multiple gain-of-function and loss-of-function strains can therefore be generated on a time scale not previously achievable. These strains can then be screened for clinically relevant abnormalities. We demonstrate the flexibility and broad applicability of the FAST system by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

Original languageEnglish
Pages (from-to)770-773
Number of pages4
JournalBiological Psychiatry
Volume67
Issue number8
DOIs
Publication statusPublished - 2010 Apr 15
Externally publishedYes

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Keywords

  • Animal model
  • conditional modulation of gene expression
  • developmental change
  • gene targeting
  • genetics
  • mouse

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Tanaka, K. F., Ahmari, S. E., Leonardo, E. D., Richardson-Jones, J. W., Budreck, E. C., Scheiffele, P., Sugio, S., Inamura, N., Ikenaka, K., & Hen, R. (2010). Flexible Accelerated STOP Tetracycline Operator-Knockin (FAST): A Versatile and Efficient New Gene Modulating System. Biological Psychiatry, 67(8), 770-773. https://doi.org/10.1016/j.biopsych.2009.12.020