These VMD2-Cre-RPE transgenic mice have a tetracycline (doxycycline) inducible Cre-mediated recombination system that is specific for the retinal pigmented epithelium (RPE). The tetO-PhCMV-cre transgenic construct contains cre recombinase under the control of the tetO, tetracycline-responsive regulatory element and the PVMD2-rtTA transgenic construct contains the reverse tetracycline-controlled transactivator, rtTA (Tet-On), under the control of the human BEST1, bestrophin 1, gene promoter. Mice hemizygous for the transgenic inserts are viable and fertile. The Donating Investigator expects homozygotes to be viable and fertile. Homozygous viability/fertility has not been tested (January 2019).When crossed to a beta-galactosidase expressing reporter strain (R26R reporter mice), tetracycline (doxycycline)-inducible Cre recombinase activity was detected in retinal pigmented epithelial cells. Weak reporter expression in the optic nerve was also detected. A very slight amount of non-induced "leaky" reporter expression is detected in a few RPE cells. While induction at embryonic day 7 to 8 did not result in productive Cre recombinase activity, induction at embryonic day 9 to 10 results in detectable reporter expression in the RPE. The strongest Cre recombinase activity is obtained with induction between embryonic day 17 and postnatal day 5 in mice induced via doxycycline diet fed to mothers. Induction by direct doxycycline feeding to young mice at postnatal day 4 results in peak Cre recombinase activity levels, which corresponds to the highest level of endogenous Best1 and human BEST1 mRNA expression at about postnatal day 4. Induction of Cre recombinase is possible up to at least 2 months of age. Transgene expression in 10 month old transgenic mice that had received doxycycline treatment at weaning age does not alter RPE cell number or electroretinography (ERG) characteristics, and photoreceptor degeneration was not detected.

VMD2-Cre-RPE transgenic mice have Tet-inducible/controllable expression of Cre recombinase directed to retinal pigmented epithelium. These mice may be useful for generating tissue specific-targeted mutants for studying gene function in retinal pigmented epithelium, especially in relation to retinal and choroidal diseases.

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