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First published online 2 December 2004
doi: 10.1242/dev.01551
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v integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death
1 Center for Cancer Research, Massachusetts Institute of Technology, 40 Ames
Street, E17-227, Cambridge, MA 02139, USA
2 Medical Research Council and University of Edinburgh Center for Inflammation
Research, Teviot Place, Edinburgh EH8 9AG, UK
3 Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
4 Windeyer Institute for Medical Sciences, University College London, 46
Cleveland Street, London W1T 4JF, UK
Author for correspondence (e-mail:
rohynes{at}mit.edu)
Accepted 28 October 2004
Mouse embryos genetically null for all 
v integrins develop
intracerebral hemorrhage owing to defective interactions between blood vessels
and brain parenchymal cells. Here, we have used conditional knockout
technology to address whether the cerebral hemorrhage is due to primary
defects in vascular or neural cell types. We show that ablating v
expression in the vascular endothelium has no detectable effect on cerebral
blood vessel development, whereas deletion of v expression in central
nervous system glial cells leads to embryonic and neonatal cerebral
hemorrhage. Conditional deletion of v integrin in both central nervous
system glia and neurons also leads to cerebral hemorrhage, but additionally to
severe neurological defects. Approximately 30% of these mutants develop
seizures and die by 4 weeks of age. The remaining mutants survive for several
months, but develop axonal deterioration in the spinal cord and cerebellum,
leading to ataxia and loss of hindlimb coordination. Collectively, these data
provide evidence that v integrins on embryonic central nervous system
neural cells, particularly glia, are necessary for proper cerebral blood
vessel development, and also reveal a novel function for v integrins
expressed on axons in the postnatal central nervous system.
Key words: Cerebral hemorrhage, Spastic paraparesis, Ataxia, Mouse
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