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

在这项研究中，我们首先检测了酪氨酸激酶受体mRor1和mRor2在小鼠发育过程中的表达模式。研究发现，在小鼠发育过程中，mRor1和mRor2的时空表达受到差异调控。mRor1表达于肢芽（近端）、鳃弓、肺、心脏和神经系统的限制性区域，而mRor2表达于肢芽（远端）、尾芽、体（皮肌瘤）、肺、心脏和神经系统（前脑、中脑）。为了阐明mRor1和mRor2的功能，我们建立了缺乏mRor1或mRor2表达的突变小鼠（敲除小鼠），并分析了这些突变小鼠的表型。mRor1和mRor2突变小鼠出生后分别在24小时和6小时内死亡，但其表型不同。mRor1突变小鼠在外观上没有表现出异常，但它们因进行性肺功能障碍而死亡。另一方面，mRor2突变小鼠表现出严重的紫绀（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mRor2突变小鼠中，其前肢和后肢远端部分存在成骨功能障碍（骨化）。此外，还观察了肋骨的融合和椎骨的畸形。如上所述，虽然mRor1突变小鼠的骨骼系统没有出现明显的异常，但我们发现mRor1/mRor2突变小鼠（mRor1/mRor2双敲除小鼠）的骨骼异常比mRor2突变小鼠严重。综上所述，我们的研究结果表明，mRor2和mRor1在发育过程中骨骼系统的形成中起着至关重要的作用。

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.