主动脉动脉瘤通常情况下不易察觉，然而，一旦发生破裂，往往会危及患者生命。胸主动脉动脉瘤具有家族遗传性，其中的马凡综合征主动脉瘤主要是由于TGF-β信号异常活化引起的，在马凡综合征小鼠模型内抑制TGF-β信号可以缓解动脉瘤。在其它遗传性胸主动脉动脉瘤内，可以检测到TGF-β受体I和II的突变。在小鼠平滑肌细胞剔除TGF-β受体II，小鼠虽有动脉瘤的表现，但是小鼠胚胎后期死亡。因此，急需建立一个合适的动物模型来研究TGF-β信号和动脉瘤发生的关系。我们利用Cre-loxP策略，交配实验室建立的SMA-Cre小鼠和TGF-β受体II、Smad4条件基因剔除小鼠，得到了出生后存活的在主动脉平滑肌细胞特异性剔除TGF-β受体II、Smad4的小鼠，小鼠很早就有动脉瘤的表型。本项目拟对这两种动脉瘤小鼠模型进行表型分析，揭示TGF-β信号异常导致动脉瘤的发病机理，寻找和测试有效治疗动脉瘤的方法。

The aortic aneurysm usually has no any symptoms, however, once it ruptured, it will cause the death of patients. The thoracic aortic aneurysm (TAA) is associated with hereditary factors. Marfan syndrome (MFS), caused by the abnormal activated TGF-beta signals, is one of familial genetic TAA. The aneurysm in the MFS mouse model can be treated by inhibiting the TGF-beta signals. There is mutation on the TGF-beta receptor I or II (TGFBRI or TGFBRII) detected in other heritable TAA. Although the mice with vascular smooth muscle cell-specific deletion of TGFBRII shows the aortic aneurysm, it died during the embryonic late stage. Therefore, the appropriate mouse model is appealed to study the relationship between TGF-beta signals and aneurysm. Using the Cre-loxP system, SMA-Cre transgenic mice and conditional TGFBRII or Smad4 targeting mice were mated to get the aortic smooth muscle cell-specific TGFBRII or Smad4 deletion mice. Our priliminary data shows that the compound mutant mice survived after birth, and aneurysm was developed very early. In this project, we will focus on describing the phenotype of aneurysm, disclosing the underlying mechanism, and testing the effective ways to treat the aneurysm in our mice model.