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

Cite this

Kerr, L. E., McGregor, A. L., Amet, L. E. A., Asada, T., Spratt, C., Allsopp, T. E., Harmar, A. J., Shen, S., Carlson, G., Logan, N., Kelly, J. S., & Sharkey, J. (2004). Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia. Cell Death and Differentiation, 11, 1102-1111. https://doi.org/10.1038/sj.cdd.4401449