title: Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.
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 wild-type littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults.
authors.affiliation: Fujisawa Institute of Neuroscience in Edinburgh, University of Edinburgh, Edinburgh EH8 9JZ, UK. Lorraine.Kerr@ed.ac.uk
authors.forename: L E
authors.initials: LE
authors.lastname: Kerr
authors.forename: A L
authors.initials: AL
authors.lastname: McGregor
authors.forename: L E A
authors.initials: LE
authors.lastname: Amet
authors.forename: T
authors.initials: T
authors.lastname: Asada
authors.forename: C
authors.initials: C
authors.lastname: Spratt
authors.forename: T E
authors.initials: TE
authors.lastname: Allsopp
authors.forename: A J
authors.initials: AJ
authors.lastname: Harmar
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.forename: G
authors.initials: G
authors.lastname: Carlson
authors.forename: N
authors.initials: N
authors.lastname: Logan
authors.forename: J S
authors.initials: JS
authors.lastname: Kelly
authors.forename: J
authors.initials: J
authors.lastname: Sharkey
mesh_terms: 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
chemical_list: C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases