Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.

Autor: Kerr LE; Fujisawa Institute of Neuroscience in Edinburgh, University of Edinburgh, Edinburgh EH8 9JZ, UK. Lorraine.Kerr@ed.ac.uk, McGregor AL, Amet LE, Asada T, Spratt C, Allsopp TE, Harmar AJ, Shen S, Carlson G, Logan N, Kelly JS, Sharkey J
Jazyk: angličtina
Zdroj: Cell death and differentiation [Cell Death Differ] 2004 Oct; Vol. 11 (10), pp. 1102-11.
DOI: 10.1038/sj.cdd.4401449
Abstrakt: 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.
Databáze: MEDLINE