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Vol. 15, No. 12, pp. 1506-1517, June 15, 2001
Department of Neuroscience, University of Virginia,
Charlottesville, Virginia 22908, USA
We report the successful transfer of a fully functional
lac operator-repressor gene regulatory system to the mouse.
The key component is a lac repressor transgene that resembles a
typical mammalian gene both in codon usage and structure and expresses functional levels of repressor protein in the animal. We used the
repressor to regulate the expression of a mammalian reporter gene
consisting of the tyrosinase promoter embedded with three short
lac operator sequences and the tyrosinase coding sequence. Pigmentation of the mouse was controlled by the interaction of the
lac repressor with the regulatable Tyrosinase transgene
in a manner that was fully reversible by the lactose analog IPTG. Direct control of mammalian promoters by the lac repressor
provides tight, reversible regulation, predictable levels of
de-repressed expression, and the promise of reversible control of the
endogenous genome.
[Key Words: lac repressor; gene regulation; transgenic mice; tyrosinase; pigmentation; albino]
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