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Michelle A. Chang, James W. Horner, Bruce R. Conklin, Ronald A. DePinho, Dean Bok, Donald J. Zack; Tetracycline-Inducible System for Photoreceptor-Specific Gene Expression. Invest. Ophthalmol. Vis. Sci. 2000;41(13):4281-4287.
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purpose. To develop a system for inducible photoreceptor-specific gene
expression in transgenic mice. The tetracycline regulatory system was
chosen because it possesses the useful property of direct control of
gene expression through use of an exogenous agent, doxycycline, a
methods. Transgenic mice were generated that carried the reverse
tetracycline-controlled transactivator under the control of the
photoreceptor-specific promoters for rhodopsin and interphotoreceptor
retinoid-binding protein. These animals were crossed with transgenic
mice carrying the lacZ reporter gene under control of the tetracycline
operator cassette, creating doubly transgenic mice. Doxycycline was
administered to induce expression of the reporter gene. Reporter assays
were then performed to evaluate lacZ expression.
results. Doxycycline administration led to photoreceptor-specific expression of
the lacZ reporter gene in the doubly transgenic mice. X-gal staining
was restricted to photoreceptor inner segments and synaptic termini.
Induction could be achieved by addition of the drug to the animals’
drinking water or by intravitreal injection. Induction was noted within
24 hours of doxcycline administration. Because of variability among
animals, there was an approximate correlation, but not a clean
dose–response curve relating drug dose to level of reporter
conclusions. A transgenic system for inducible photoreceptor-specific gene
expression has been developed. This system is currently being exploited
to study the effects of regulated expression of genes of biological
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