Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
J Cereb Blood Flow Metab. 2022 Dec;42(12):2230-2244. doi: 10.1177/0271678X221105995. Epub 2022 Jun 10.
Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes (, and ) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations. Here, we employed the Dre-Cre dual recombinase system to specifically delete genes in brain endothelial cells. In this new series of CCM mouse models, robust CCM lesions now develop in the cerebrum. The survival curve and lesion burden analysis revealed that deletion causes modest CCM lesions with a median life expectance of ∼10 months and gene deletion leads to the most severe CCM lesions with median life expectance of ∼2 months. The extended lifespan of these mutant mice enables their utility in behavioral analyses of neurologic deficits in adult mice, and allow the development of methods to quantify lesion burden in mice over time and also permit longitudinal drug testing in live animals.
脑海绵状血管畸形（CCM）是一种脑部血管疾病，可导致受影响个体发生中风、脑出血和神经功能缺损。三个基因（ 、 和 ）的功能丧失性突变可导致 CCM 疾病。已经开发了多种 CCM 疾病的小鼠模型，但它们各自都存在各种局限性。在这里，我们使用 Dre-Cre 双重组酶系统特异性地在脑内皮细胞中删除 基因。在这个新的 CCM 小鼠模型系列中，大脑中现在出现了强有力的 CCM 病变。生存曲线和病变负担分析表明， 缺失导致适度的 CCM 病变，中位预期寿命约为 10 个月，而 基因缺失导致最严重的 CCM 病变，中位预期寿命约为 2 个月。这些突变小鼠的延长寿命使其可用于成年小鼠神经功能缺损的行为分析，并允许开发随时间定量分析小鼠病变负担的方法，也允许对活体动物进行纵向药物测试。
