Mleynek Tara M, Chan Aubrey C, Redd Michael, Gibson Christopher C, Davis Chadwick T, Shi Dallas S, Chen Tiehua, Carter Kandis L, Ling Jing, Blanco Raquel, Gerhardt Holger, Whitehead Kevin, Li Dean Y
Department of Molecular Medicine, Department of Oncological Sciences.
Flourescence Imaging Core.
Hum Mol Genet. 2014 Dec 1;23(23):6223-34. doi: 10.1093/hmg/ddu342. Epub 2014 Jul 2.
Cerebral cavernous malformation (CCM) is a disease of vascular malformations known to be caused by mutations in one of three genes: CCM1, CCM2 or CCM3. Despite several studies, the mechanism of CCM lesion onset remains unclear. Using a Ccm1 knockout mouse model, we studied the morphogenesis of early lesion formation in the retina in order to provide insight into potential mechanisms. We demonstrate that lesions develop in a stereotypic location and pattern, preceded by endothelial hypersprouting as confirmed in a zebrafish model of disease. The vascular defects seen with loss of Ccm1 suggest a defect in endothelial flow response. Taken together, these results suggest new mechanisms of early CCM disease pathogenesis and provide a framework for further study.
脑海绵状血管畸形（CCM）是一种血管畸形疾病，已知由三个基因之一CCM1、CCM2或CCM3的突变引起。尽管有多项研究，但CCM病变发生的机制仍不清楚。我们使用Ccm1基因敲除小鼠模型研究了视网膜早期病变形成的形态发生，以便深入了解潜在机制。我们证明病变在一个固定的位置和模式下发展，在斑马鱼疾病模型中证实，在此之前有内皮细胞过度出芽。Ccm1缺失时出现的血管缺陷表明内皮血流反应存在缺陷。综上所述，这些结果提示了CCM疾病早期发病机制的新观点，并为进一步研究提供了框架。
