Neuron-specific transgene expression of Bcl-XL but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice.
Protective effects after focal cerebral ischemia were assessed in transgenic mice that overexpress in a neuron-specific fashion mouse Bcl-XL or human Bcl-2. Both Bcl genes were under the control of the same mouse Thy-1 regulatory sequences resulting in very similar expression patterns in cortical neurons. Furthermore, these sequences direct lateonset (i.e. around birth) expression in brain, thus minimizing effects of transgene expression during brain development. Effects on infarct volume were measured using MRI after permanent occlusion of the middle cerebral artery (MCA). When compared to their non-transgenic littermates, Thy1mbcl-XL mice showed a significant 21% reduction in infarct size whereas Thy1hbcl-2 mice did not reveal any reduction. These findings suggest a selective protective advantage of Bcl-XL as compared with Bcl-2 in this mouse model for human stroke.
Novartis Pharma AG, Basle, Switzerland. christoph.wiessner@pharma.novartis.com
C
C
Wiessner
P R
PR
Allegrini
K
K
Rupalla
D
D
Sauer
T
T
Oltersdorf
A L
AL
McGregor
S
S
Bischoff
B W
BW
Böttiger
H
H
van der Putten
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D002536:Cerebral Arteries; D015870:Gene Expression; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein