TAILIEUCHUNG - Báo cáo khoa học: Recent insights into cerebral cavernous malformations: animal models of CCM and the human phenotype

Cerebral cavernous malformations are common vascular lesions of the cen-tral nervous system that predispose to seizures, focal neurologic deficits and potentially fatal hemorrhagic stroke. Human genetic studies have iden-tified three genes associated with the disease and biochemical studies of these proteins have identified interaction partners and possible signaling pathways. | MINIREVIEW Recent insights into cerebral cavernous malformations animal models of CCM and the human phenotype Aubrey C. Chan1 Dean Y. Li1 2 Michel J. Berg3 and Kevin J. Whitehead1 2 1 Molecular Medicine Program University of Utah Salt Lake City UT USA 2 Division of Cardiology University of Utah Salt Lake City UT USA 3 Department of Neurology University of Rochester MedicalCenter NY USA Keywords animal model cavernous angioma CCM CCM2 cerebralcavernous malformation Krit1 mouse model OSM PDCD10 zebrafish Correspondence K. J. Whitehead Molecular Medicine Program University of Utah 15 N. 2030 East Salt Lake City UT 84112 USA Fax 1 801 585 0701 Tel 1 801 585 1694 E-mail Received 8 September 2009 revised 5 November 2009 accepted 6 November 2009 Cerebral cavernous malformations are common vascular lesions of the central nervous system that predispose to seizures focal neurologic deficits and potentially fatal hemorrhagic stroke. Human genetic studies have identified three genes associated with the disease and biochemical studies of these proteins have identified interaction partners and possible signaling pathways. A variety of animal models of CCM have been described to help translate the cellular and biochemical insights into a better understanding of disease mechanism. In this minireview we discuss the contributions of animal models to our growing understanding of the biology of cavernous malformations including the elucidation of the cellular context of CCM protein actions and the in vivo confirmation of abnormal endothelial cellcell interactions. Challenges and progress towards developing a faithful model of CCM biology are reviewed. doi Introduction Cerebral cavernous malformation CCM is a common vascular disease consisting of clusters of dilated thinwalled vessels lacking smooth muscle support and prone to hemorrhage. They are found in 1 in 200-250 individuals in the general population 1 2 . Although .

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