TETRACYCLINE REGULATED EXPRESSION OF AN ACTIVATED FORM OF CaM KINASEII IN THE FOREBRAIN OF TRANSGENIC MICE

by

Mark Mayford, L. Wang, K. Podsypanina, and Eric Kandel

Summary
One of the drawbacks of using genetically modified mice in the study of learning and memory is the lack of temporal control over the expression of the genetic change (Mayford et al., 1995). Recently, Furth et al. (1994) have described a binary system for the regulation of transgene expression in peripheral tissue using tetracycline. We have used this system to drive expression of an activated form of CaM kinase II, that is Ca2+ -independent due to the introduction of an aspartate at amino acid 286. Previous studies have shown that expression of this mutant form of the kinase shifts the response of hippocampal synapses to low-frequency trains in the 5-10 Hz range, so that LTD is enhanced and LTP is reduced (Mayford et al., CEll, in press). Using the tetracycline system combined with the CaMKIIa promoter, we generated mice that show strong transgene expression, which is limited to specific regions of the forebrain. Preliminary results indicate that transgene expression can be blocked by the administration of tetracycline analogs to the mice. The use of this system should allow the developmental consequences of acute expression at both the electrophysiological and behavioral level.

Keywords:

contributed by Mark Mayford
in July 1996

Mark Mayford
Chief, Tumor Growth Factor Section
Columbia University
New York, NY

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