Functional Study of Ankrd17 in Vascular Development

• Main Authors: Yen-Jung Chiu, 邱彥蓉
• Other Authors: Yu-Ting Yan
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/25065922884135331026

碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 101 === Ankyrin repeat domain containing protein 17 (Ankrd17) gene encodes a ubiquitously expressed protein with two clusters of ankyrin repeats. The Ankrd17-deficient (Ankrd17-/-) mice die around embryonic day (E) 11.5 due to vascular development defects with severe hemorrhage. The blood vessels of Ankrd17-/- embryo has a normal pattern of endothelial cells (ECs) but less vascular smooth muscle cells (vSMCs) surround ECs compare with that in wild-type. These results suggest that Ankrd17 might play a functional role in regulating cell differentiation or migration of vSMCs. Using a gene knockdown approach in C3H/10T1/2 cells, I found that Ankrd17 could repress smooth muscle α-actin (α-SMA) expression but it was not caused by regulating the transcriptional activity of α-SMA promoter. Furthermore, downregulation of Ankrd17 could suppress the proliferation but not the migration ability in C3H/10T1/2 cells. Finally, I generated Ankrd17 SMC and EC-specific conditional knockout (CKO) mice to examine the role of Ankrd17 in embryonic vascular development. Interestingly, Ankrd17 CKO generated by SM22-, Tie2- or Mesp1-Cre did not cause vascular defect phenotypes as that in conventional knockout mice. Put together, my study provided some clues for the relationship between Ankrd17 and vSMC, but the biological and biochemical function of Ankrd17 in regulating vascular development still needs more works to investigate.