Mos-iCsp3 transgenic mice have a CMV promoter directing expression of a floxed-lacZ-STOP cassette followed by two tandem FK506-binding sites (Fvs) and a downstream human Caspase 3 (Casp3) gene. Hemizygous Mos-iCsp3 mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Caspase 3 is a member of the cysteine-aspartic acid protease family of enzymes which are integral to apoptosis pathways. Inactive until cleaved by an initiator enzyme, Caspase 3 is processed at conserved aspartic residues and is activated by the formation of dimers. In this transgenic strain, a STOP cassette is present, flanked by a loxH site and a loxP site, preventing inducible Caspase 3 expression and allowing for widespread lacZ staining. LacZ staining in founder line 17 is seen in the spinal cord, muscle, pancreas, skin, and portions of the brain and skull. The presence of both a loxH site and a loxP site causes reduced cre efficiency, resulting in mosaic expression of Caspase 3 after cre-mediated recombination. This inducible Caspase 3 is bound to 2 tandem FK506-binding sites which act to bring 2 monomers together after induction by the FK506 analogue, AP20187. This dimerization activates Caspase 3 in cre-expressing cells, resulting in cell death. These mice may be useful for cell ablation of specific cell types and as a model of degenerative diseases such as Parkinson's Disease, type 1 diabetes, alopecia, and deafness.
