Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus
Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus
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DOI：
10.1007/pl00008193
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Kern, MJ
中科院分区：
文献类型：
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作者：
Bergwerff, M;Gittenberger-de Groot, AC;Kern, MJ
Prx 1（MHox）和Prx 2（S8）是非簇同源盒基因，在整个胚胎发生中以复杂的、主要是间充质特异性的模式表达。先前的表达模式和基因靶向小鼠揭示了Prx 1在骨骼发生中的主要作用。此外，在发育中的心血管系统中报告了两种Prx基因的特异性和高表达，主要是在心脏的预期结缔组织和大动脉和静脉中。我们检查了先前产生的基因靶向小鼠的胚胎。Prx 2-/-突变体是可行的，并没有表现出心血管畸形。Prx 1-/-和Prx 1/Prx 2-组合无效突变体的心内形态在整个发育过程中也表现正常。然而，Prx-1-/-和Prx 1/Prx 2双无效突变体显示血管异常，除了错误定向和延长的动脉导管外，主动脉弓的异常定位和笨拙的弯曲，并且在7个组合突变体中的2个中，异常的食管后右锁骨下动脉。一般来说，所有的大动脉似乎有点曲折地穿过周围的间质。所有突变体的血管组织学和血管壁厚度均正常。Prx 1-/- ann Prx双基因靶向小鼠显示了类似的血管异常谱，但双突变体似乎受到更严重的影响。目前的研究结果表明，其他基因可能会弥补心脏中Prx的损失，但相比之下，我们的数据支持Prx在血管和血管周围基质的发展中的作用。
Prx1 (MHox) and Prx2 (S8) are non-clustered homeobox genes that are expressed in a complex, mostly mesenchyme-specific pattern throughout embryogenesis. The expression pattern and gene-targeted mice previously revealed a major role for Prx1 in skeletogenesis. In addition, specific and high expression of both Prx genes was reported in the developing cardiovascular system, predominantly in prospective connective tissues of the heart and in the great arteries and veins. We examined embryos of previously generated gene-targeted mice. Prx2-/- mutants were viable and did not show cardiovascular malformations. Intracardiac morphology of Prx1-/- and Prx1/Prx2-combined null mutants also appeared normal throughout development. However, the Prx-1-/- and Prx1/Prx2 double-null mutants showed a vascular abnormality with an abnormal positioning and awkward curvature of the aortic arch in addition to a misdirected and elongated ductus arteriosus, and in two of seven combined mutants, an anomalous retro-oesophageal right subclavian artery. Generally, all great arteries appeared to run somewhat tortuously through the surrounding mesenchyme. The vascular histology and vessel wall thickness were normal in all mutants. Prx1-/- ann Prx double-gene-targeted mice revealed similar spectra of vascular anomalies, but double mutants appeared to be more seriously affected. The current findings suggest that other genes may compensate for the loss of Prx in the heart, but, in contrast, our data support a role for Prx in the development of vascular and perivascular matrix.