Abstract
Caspase 3 activation has been implicated in cell death following a number of neurodegenerative insults. To determine whether caspase genes can affect the susceptibility of cells to neurodegeneration, a transgenic mouse line was created, expressing human caspase 3 under control of its own promoter. The human gene was regulated by the murine homeostatic machinery and human procaspase 3 was expressed in the same tissues as mouse caspase 3. These novel transgenic mice appeared phenotypically and developmentally normal and survived in excess of 2 years. Behavioural assessment using the 5-choice serial reaction time task found no differences from wild-type littermates. Caspase activity was found to be tightly regulated under physiological conditions, however, significantly larger lesions were obtained when transgenic mice were subjected to focal cerebral ischaemia/reperfusion injury compared to wildtype littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults.
Original language | English |
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Pages (from-to) | 1102-1111 |
Number of pages | 10 |
Journal | Cell Death and Differentiation |
Volume | 11 |
DOIs | |
Publication status | Published - 2004 |
Keywords
- caspase 3
- transgenic
- apoptosis
- ischaemia
- stroke
- neurodegeneration
- 5-CSRTT
- TRAUMATIC BRAIN-INJURY
- INTERLEUKIN-1-BETA CONVERTING-ENZYME
- CELL-DEATH
- PARKINSONS-DISEASE
- IN-VIVO
- CASPASE-3-DEFICIENT MICE
- DECREASED APOPTOSIS
- NEURONAL APOPTOSIS
- PRECURSOR PROTEIN
- CYSTEINE PROTEASE