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. 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.
Albert Edge, Massachusetts Eye and Ear
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 14 is seen in the eye, kidney, pancreas, skin, thymus, and portions of the brain. 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.
The Mos-iCsp3 transgene was designed with (from 5' to 3') a CMV promoter, a loxH site, a β-galactosidase (lacZ) gene, a V5-tag (derived from the paramyxovirus of simian virus 5 (SV5)), a 6x-histidine-tag, a polyadenylation (polyA) signal, and a loxP site. This floxed-lacZ-STOP cassette was followed by a myristoylation sequence, two tandem FK506-binding sites (Fvs), a human Caspase 3 (Casp3) gene, a haemagglutinin (HA) tag, and a second (polyA) signal. The transgene was microinjected into fertilized C57BL/6 X C3H/HeN F1 oocytes, and mice from founder line 14 were bred to C57BL/6J mice for at least 8 generations to establish a colony. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664).
|Expressed Gene||CASP3, caspase 3, human|
|Site of Expression|
|Allele Name||transgene insertion 14, Albert Edge|
|Allele Type||Transgenic (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence, Humanized sequence)|
|Gene Symbol and Name||Tg(CMV-CASP3)14Edge, transgene insertion 14, Albert Edge|
|Promoter||CMV, cytomegalovirus, human|
|Expressed Gene||CASP3, caspase 3, human|
|Strain of Origin||(C57BL/6 x C3H/HeN)F1|
|Molecular Note||The Mos-iCsp3 transgene was designed with (from 5' to 3') a CMV promoter, a loxH site, a beta-galactosidase (lacZ) gene, a V5-tag (derived from the paramyxovirus of simian virus 5 (SV5)), a 6x-histidine-tag, a polyadenylation (polyA) signal, and a loxP. This floxed-lacZ-STOP cassette was followed by a myristoylation sequence, two tandem FK506-binding sites (Fvs), a human Caspase 3 (CASP3) gene, a haemagglutinin (HA) tag, and a second (polyA) signal. Lines 14 and 17 were generated.|
|Mutations Made By|| |
Albert Edge, Massachusetts Eye and Ear
When maintaining a live colony, hemizygous mice may be bred to wildtype (non-carriers) from the colony or to C57BL/6J inbred mice (Stock No. 000664).
When using the B6.Cg-Tg(CMV-CASP3)14Edge/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016882 in your Materials and Methods section.
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