TetTag

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The TetTag mouse is a bi-transgenic mutant that expresses a persistent marker (e.g. beta-galactosidase) under control of the immediate early gene Fos. This strain provides a tool that allows the inducible stable labeling of activated neurons.^[1]

Two independently generated transgenic strains were crossed to produce the TetTag strain. In the first transgenic construct, the tetracycline-controlled transactivator (tTA) protein and a two hour half-life Green Fluorescent Protein (shEGFP) are expressed under the direction of the fos minimal promoter. The second transgenic construct expresses a nuclear-localizing beta-galactosidase gene and the tetracycline regulated transactivator (tTA) under the control of the TetO (tetracycline-responsive regulatory element).

In this system, doxycycline administration prevents expression of beta-galactosidase in neurons. The strain is maintained with doxycycline-containg food to prevent beta-galactosidase expression. In the absence of doxycycline, tau-LacZ is induced in active neurons. Using viral delivery, it is also possible to express a different protein (e.g. channelrhodopsin) under TetO control.

The TetTag mouse allows researchers to label activated neurons during a learning experiment (e.g. fear conditioning^[3], water maze training^[4]). When the memory is later retrieved, the acutely activated neurons can be labeled by immunohistochemistry against immediate early genes (e.g. Zif, see figure). These experiments test whether the same neurons are responsible for storing and retrieving a memory, a key question to understand the engram.

Several TetTag strains are available from the Jackson Laboratory.