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functional analyses of receptor tyrosine kinases mRor1 and mRor2 that are involved in the development of the nervous system.

参与神经系统发育的受体酪氨酸激酶 mRor1 和 mRor2 的功能分析。

基本信息

批准号：
10470030
负责人：
MINAMI Yasuhiro
金额：
$ 3.65万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470030/
关键词：
Ror1, 2 receptor tyrosine kinases development of the nervous system neuronal differentiation knock-out mice VSD pulmonary dysfunction dysplasia of the skeletal system 染色体マッピング連鎖解析

项目摘要

In this study, we first examined expression patterns of the receptor tyrosine kinases, mRor1 and mRor2, during mouse development. It was found that spatio-temporal expressions of mRor1 and mRor2 are differentially regulated during mouse development. mRor1 was expressed in limb buds (proximal part), branchial arches, lung, heart, and restricted regions of the nervous system, while mRor2 expression was detected in limb buds (distal part), tail buds, somites (dermatomyotomes), lung, heart, and the nervous system (forebrain, midbrain). To elucidate the functions of mRor1 and mRor2, we have established mutant mice (knock-out mice) lacking the expression of mRor1 or mRor2, and analyzed phenotypes of these mutant mice. Both mRor1 and mRor2 mutant mice died after birth within 24 hrs and 6 hrs, respectively, yet their phenotypes were different. mRor1 mutant mice did not exhibit abnormalities in their appearance, but they died due to a progressive pulmonary dysfunction. On the other hand, mRor2 mutant mice exhibited severe cyanosis (due to pulmonary dysfunction and VSD) with abnormal appearances in their skeletal system, and died within 6 hrs after birth. In mRor2 mutant mice, there were dysfunctions of osteogenesis (ossification) in their fore- and hind-limbs at distal parts. In addition, the fusion of their ribs and deformity of their vertebrae were also observed. As mentioned above, although mRor1 mutant mice did not exhibit apparent abnormality in their skeletal systems, it was found that the skeletal abnormalities in mRor1/mRor2 mutant mice (mRor1/mRor2 double knock-out mice) were severer than those observed in mRor2 mutant mice. Taken together, our findings indicate that mRor2 as well as mRor1 play crucial roles in the formation of the skeletal system during development.

在这项研究中，我们首先研究了受体酪氨酸激酶，mRor 1和mRor 2，在小鼠发育过程中的表达模式。结果发现，在小鼠发育过程中，mRor 1和mRor 2的时空表达受到差异调节。mRor 1在肢芽（近端部分）、鳃弓、肺、心脏和神经系统的限制区域中表达，而mRor 2在肢芽（远端部分）、尾芽、体节（皮肌节）、肺、心脏和神经系统（前脑、中脑）中表达。为了阐明mRor 1和mRor 2的功能，我们建立了缺乏mRor 1或mRor 2表达的突变小鼠（基因敲除小鼠），并分析了这些突变小鼠的表型。mRor 1和mRor 2突变小鼠分别在出生后24小时和6小时内死亡，但它们的表型不同。mRor 1突变小鼠在外观上没有表现出异常，但它们由于进行性肺功能障碍而死亡。另一方面，mRor 2突变小鼠表现出严重的发绀（由于肺功能障碍和VSD），骨骼系统出现异常，并在出生后6小时内死亡。在mRor 2突变小鼠中，在其前肢和后肢的远端部分存在成骨功能障碍（骨化）。此外，还观察到肋骨融合和椎骨畸形。如上所述，虽然mRor 1突变小鼠在其骨骼系统中没有表现出明显的异常，但发现mRor 1/mRor 2突变小鼠（mRor 1/mRor 2双敲除小鼠）中的骨骼异常比mRor 2突变小鼠中观察到的骨骼异常更严重。综上所述，我们的研究结果表明，mRor 2以及mRor 1在骨骼系统发育过程中的形成中起着至关重要的作用。