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Kerr, L.E.a and McGregor, A.L.a and Amet, L.E.A.a and Asada, T.a e and Spratt, C.a and Allsopp, T.E.a c and Harmar, A.J.b and Shen, S.b d and Carlson, G.a and Logan, N.a and Kelly, J.S.a and Sharkey, J.a
Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia
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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 wild-type littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults. © 2004 Nature Publishing Group All rights reserved.
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