Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.
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.
Kerr
L E
LE
Fujisawa Institute of Neuroscience in Edinburgh, University of Edinburgh, Edinburgh EH8 9JZ, UK. Lorraine.Kerr@ed.ac.uk
McGregor
A L
AL
Amet
L E A
LE
Asada
T
T
Spratt
C
C
Allsopp
T E
TE
Harmar
A J
AJ
Shen
S
S
Carlson
G
G
Logan
N
N
Kelly
J S
JS
Sharkey
J
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001522:Behavior, Animal; D053148:Caspase 3; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases