| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Research Abstract |
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.
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