Age-dependent lethality in novel transgenic mouse models of central nervous system arteriovenous malformations

Ian Milton, Dan Ouyang, Caitlin J. Allen, Nathan Eugene Yanasak, James R Gossage, Cargill Herley Alleyne, Tsugio Seki

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background and Purpose-The lack of an appropriate animal model has been a limitation in studying hemorrhage from arteriovenous malformations (AVMs) in the central nervous system. Methods-Novel mouse central nervous system AVM models were generated by conditionally deleting the activin receptor-like kinase (Alk1; Acvrl1) gene with the SM22-Cre transgene. All mice developed AVMs in their brain and/or spinal cord, and >80% of them showed a paralysis or lethality phenotype due to internal hemorrhages during the first 10 to 15 weeks of life. The mice that survived this early lethal period, however, showed significantly reduced lethality rates even though they carried multiple AVMs. Results-The age-dependent change in hemorrhage rates allowed us to identify molecular factors uniquely upregulated in the rupture-prone AVM lesions. Conclusions-Upregulation of angiopoietin 2 and a few inflammatory genes were identified in the hemorrhage-prone lesions, which may be comparable with human pathology. These models will be an exceptional tool to study pathophysiology of AVM hemorrhage.

Original languageEnglish (US)
Pages (from-to)1432-1435
Number of pages4
JournalStroke
Volume43
Issue number5
DOIs
StatePublished - May 1 2012

Fingerprint

Nervous System Malformations
Arteriovenous Malformations
Transgenic Mice
Central Nervous System
Hemorrhage
Activin Receptors
Angiopoietin-2
Transgenes
Paralysis
Genes
Rupture
Spinal Cord
Up-Regulation
Animal Models
Pathology
Phenotype
Brain

Keywords

  • Activin receptor-like kinase 1
  • Arteriovenous malformation
  • Hereditary hemorrhagic telangiectasia
  • Intracranial hemorrhage
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Age-dependent lethality in novel transgenic mouse models of central nervous system arteriovenous malformations. / Milton, Ian; Ouyang, Dan; Allen, Caitlin J.; Yanasak, Nathan Eugene; Gossage, James R; Alleyne, Cargill Herley; Seki, Tsugio.

In: Stroke, Vol. 43, No. 5, 01.05.2012, p. 1432-1435.

Research output: Contribution to journalArticle

Milton, Ian ; Ouyang, Dan ; Allen, Caitlin J. ; Yanasak, Nathan Eugene ; Gossage, James R ; Alleyne, Cargill Herley ; Seki, Tsugio. / Age-dependent lethality in novel transgenic mouse models of central nervous system arteriovenous malformations. In: Stroke. 2012 ; Vol. 43, No. 5. pp. 1432-1435.
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