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

L E Kerr, A L McGregor, L E A Amet, T Asada, C Spratt, T E Allsopp, A J Harmar, S Shen, G Carlson, N Logan, J S Kelly, J Sharkey

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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 languageEnglish
Pages (from-to)1102-1111
Number of pages10
JournalCell Death and Differentiation
Volume11
DOIs
Publication statusPublished - 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

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