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

Stroke; a Journal of Cerebral Circulation
Ian MiltonTsugio Seki

Abstract

The lack of an appropriate animal model has been a limitation in studying hemorrhage from arteriovenous malformations (AVMs) in the central nervous system. 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. The age-dependent change in hemorrhage rates allowed us to identify molecular factors uniquely upregulated in the rupture-prone AVM lesions. 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.

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Citations

Oct 1, 2013·Cellular and Molecular Life Sciences : CMLS·Deepak AtriMichael Simons
Apr 12, 2014·Translational Stroke Research·Wanqiu ChenHua Su
May 21, 2015·International Journal of Molecular Sciences·Jenny B LinCraig J Goergen
Dec 10, 2015·BioMed Research International·Ming XuZhiyong Qin
Mar 6, 2015·Frontiers in Genetics·Simon Tual-ChalotHelen M Arthur
Apr 30, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Hongyu TianGerard C Blobe
Sep 10, 2015·Stroke; a Journal of Cerebral Circulation·Corinne M NielsenRong A Wang
Jan 20, 2018·Cardiovascular Research·Juhana Frösen, Anne Joutel
Jun 19, 2015·Veterinary Sciences·Jude Amal Raj, Marcus Stoodley
Nov 17, 2019·International Journal of Molecular Sciences·Leandro Barbosa Do PradoHua Su
Nov 20, 2016·The Journal of Pathology·Sarah E Wetzel-StrongDouglas A Marchuk
Mar 24, 2021·Tissue & Cell·Leyla SatiJames McGrath
Mar 27, 2021·Current Opinion in Hematology·Ondine Cleaver
Mar 27, 2021·Current Opinion in Hematology·Ondine Cleaver
Jun 25, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Peipei PanHua Su
Aug 28, 2021·International Journal of Molecular Sciences·Katharina SchimmelEdda Spiekerkoetter

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