Analysis of cardiovascular anomalies in the Hoxa3 and Pax-3 homozygous null mutant mice.

Hoxa3 和 Pax-3 纯合无效突变小鼠的心血管异常分析。

基本信息

批准号：
14570026
负责人：
KAMEDA Yoko
金额：
$ 2.24万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570026/
关键词：
Hoxa3 knockout mice Connexin43-LacZ mice Third arch artery Third pharyngeal pouch Baroreceptors Neural crest cells VEGF Endothelin-1 Hoxa3ノックアウトマウス Cx43-lacZトランスジェニック・マウス総頚動脈欠損

项目摘要

Hoxa3 gene is expressed in the third pharyngeal arch and pouch and is required for development of the third arch artery in addition to the thymus, parathyroid land and carotid body. We statistically analyzed malformations of the carotid artery system in Hoxa3 homozygous mutant mice, in comparison with wild-type and heterozygous littermates. In the Hoxa3 homozygotes, the third arch artery was observed at E 10.5 but degenerated at E 11.5. Therefore the common carotid artery, the derivative of the third arch artery was absent or very short in the null mutants. The tunica media of great arteries derived from the arch arteries is formed by the ectomesenchymal neural crest cells. To assess the cause of the third arch artery regression, the Hoxa3 heterozygous mice were crossed with the connexin43-lacZ transgenic mice in which neural crest cells are specified by β-galactosidase expression. The neural crest cells normally migrated into the third pharyngeal arch and surrounded the arch artery in the null mutants as well as wild types. The expressions of VEGF_<165>, its receptors (tyrosine kinases Flt-1 and Flk-1), endothelin ET-1 and dHand which are responsible for development of embryonic blood vessels or arch arteries, were analyzed in the third arch artery of the E 10.5 Hoxa3 null mutants, in comparison with wild types, by the laser capture microdissection and real-time PCR methods. VEGF_<165> mRNA was almost lost and ET-1 mRNA was markedly reduced in the null mutants. Flk-1 mRNA expression was down-regulated whereas Flt-1 mRNA was up-regulated in the mutants. The Hoxa3 gene may ragulate the pathways of both VEGF and ET-1 systems for the third arch artery development.

Hoxa3基因在第三咽弓和咽袋中表达，是除胸腺、甲状旁腺区和颈动脉体之外的第三咽弓动脉发育所必需的。我们仔细分析了Hoxa3纯合突变小鼠的颈动脉系统畸形。在 Hoxa3 纯合子中，在 E 10.5 处观察到第三弓动脉，但在 E 处退化。 11.5. 因此，颈总动脉（第三弓动脉的衍生物）在无效突变体中不存在或非常短。源自弓动脉的大动脉中膜是由外间充质神经嵴细胞形成的。第三弓动脉退化，Hoxa3杂合子小鼠与connexin43-lacZ转基因小鼠杂交，其中神经嵴细胞由β-半乳糖苷酶表达指定。在无效突变体和野生型中，嵴细胞正常迁移到第三咽弓并包围弓动脉。VEGF_<165>、其受体（酪氨酸激酶Flt-1和Flk-1）、内皮素ET-1的表达。与野生型相比，在 E 10.5 Hoxa3 无效突变体的第三弓动脉中对负责胚胎血管或弓动脉发育的 dHand 和 dHand 进行了分析。通过激光捕获显微切割和实时PCR方法，VEGF_<165> mRNA几乎丢失，并且在无效突变体中ET-1 mRNA显着减少，而Flt-1 mRNA表达下调。 Hoxa3 基因在突变体中上调，可能调节 VEGF 和 ET-1 系统对第三弓动脉发育的影响。