TetP-PARIS-Flag mice express a flag-tagged human ZNF746 gene under the direction of the tetracycline operator (tetO). ZNF746, also known as PARIS (parkin-interacting substrate), is a transcriptional repressor. Increased expression of PARIS has been associated with the onset of Parkinson's disease (PD) due to its repression of peroxisome proliferator-activated receptor-&gamma; coactivator-1&alpha; (PGC-1&alpha; PPARGC1A) activity. Overexpression of PARIS has also been implicated in selective dopaminergic (DA) neuronal degeneration, which plays a role in the development of PD. When bred with another mouse expressing tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), tissue-specific ZNF746 expression in the resulting double mutant offspring can be regulated with tetracycline or its analog doxycycline (dox). When bred to CamKII&alpha;-tTA mice (Stock No. <a href="https://www.jax.org/strain/007004">007004</a>) to overexpress ZNF746 in the forebrain, dox-inducible expression of ZNF746 in resulting CamK-PARIS mice results in embryonic lethality. When dams and offspring are maintained on dox, offspring are viable. Dox withdrawal at 3 weeks of age leads to overexpression of PARIS at 2 weeks after withdrawal in the olfactory bulb, cortex, striatum, ventral midbrain, cerebellum, and brain stem of CamK-PARIS mice compared to littermate controls. The donating investigator states that homozygous TetP-PARIS-Flag mice are viable and fertile.

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TetP-PARIS-Flag mice express a flag-tagged human ZNF746 gene under direction of the tetracycline operator (tetO). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of ZNF746 protein may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring. These mice may be useful when studying treatments for dopaminergic neuronal degeneration in models of Parkinson's disease.

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