Thbd-flox Mouse

Thbd, also known as thrombomodulin, is part of the anticoagulant protein C-system acting at the endothelium. It is involved in anti-inflammatory and barrier-stabilizing processes, and also plays a role in angiogenesis [2].

In a mouse model where Thbd was specifically deleted in brain endothelial cells using a Cre/loxP-based system, stroke outcome worsened 48 hours after middle cerebral artery occlusion. This was due to decreased vessel diameters and impaired angiogenesis in the peri-infarct area, leading to a reduced overall vessel length 1 week after stroke induction, indicating its importance in ischemic stroke protection [2]. In another study, rare loss-of-function or non-benign missense variants of Thbd in humans were associated with an increased risk of venous thromboembolism (VTE), suggesting its role in maintaining hemostatic balance [1].

In conclusion, Thbd is crucial for maintaining hemostasis and is involved in anti-inflammatory, barrier-stabilizing, and angiogenic processes. Mouse models, especially those with conditional knockout of Thbd in specific cell types, have revealed its significance in ischemic stroke and the development of VTE, providing insights into the underlying mechanisms and potential therapeutic targets for these diseases.