Cell and Molecular Biology Department, Tulane University, New Orleans, Louisiana.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
Dev Dyn. 2020 May;249(5):666-678. doi: 10.1002/dvdy.154. Epub 2020 Feb 14.
Annexin A3 (Anxa3) is a member of the calcium-regulated, cell membrane-binding family of annexin proteins. We previously confirmed that Anxa3 is expressed in the endothelial lineage in vertebrates and that loss of anxa3 in Xenopus laevis leads to embryonic blood vessel defects. However, the biological function of Anxa3 in mammals is completely unknown. In order to investigate Anxa3 vascular function in mammals, we generated an endothelial cell-specific Anxa3 conditional knockout mouse model (Anxa3 ;Tie2-Cre).
Anxa3 ;Tie2-Cre mice are born at Mendelian ratios and display morphologically normal blood vessels during development. However, loss of Anxa3 leads to artery-vein (AV) misalignment characterized by atypical AV crossovers in the postnatal and adult retina.
Anxa3 is not essential for embryonic blood vessel formation but is required for proper parallel AV alignment in the murine retina. AV crossovers associated with Anxa3 ;Tie2-Cre mice are similar to AV intersections observed in patients with branch retinal vein occlusion (BRVO), although we did not observe occluded vessels. This new Anxa3 mouse model may provide a basis for understanding AV crossover formation associated with BRVO.
膜联蛋白 A3（Anxa3）是钙调节的细胞膜结合 annexin 蛋白家族的成员。我们之前证实 Anxa3 在脊椎动物的内皮谱系中表达，并且 Xenopus laevis 中 anxa3 的缺失导致胚胎血管缺陷。然而，Anxa3 在哺乳动物中的生物学功能尚完全未知。为了研究哺乳动物中 Anxa3 的血管功能，我们生成了内皮细胞特异性 Anxa3 条件性敲除小鼠模型（Anxa3 ;Tie2-Cre）。
Anxa3 ;Tie2-Cre 小鼠以孟德尔比例出生，在发育过程中显示出形态正常的血管。然而，Anxa3 的缺失导致动脉-静脉（AV）错位，表现为出生后和成年视网膜中典型的 AV 交叉。
Anxa3 对于胚胎血管形成不是必需的，但对于小鼠视网膜中 AV 的平行对齐是必需的。与 Anxa3 ;Tie2-Cre 小鼠相关的 AV 交叉类似于伴有视网膜分支静脉阻塞（BRVO）的患者观察到的 AV 交叉，尽管我们没有观察到闭塞的血管。这种新的 Anxa3 小鼠模型可能为理解与 BRVO 相关的 AV 交叉形成提供基础。
