Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation

Authors

  • Shigeto Takeuchi,

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Kiyoshi Takeda,

    1. Department of Biochemistry, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8131, Japan
    2. CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST), Chiyoda-ku, Tokyo 102-0081, Japan
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  • Isao Oishi,

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Masashi Nomi,

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Makoto Ikeya,

    1. Center for Molecular and Developmental Biology, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
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  • Kyoko Itoh,

    1. Department of Pathology, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Shingo Tamura,

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Takahiro Ueda,

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Toshihisa Hatta,

    1. Department of Anatomy, Shimane Medical University, 89-1, Enya-cho, Izumo 693-8501, Japan
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  • Hiroki Otani,

    1. Department of Anatomy, Shimane Medical University, 89-1, Enya-cho, Izumo 693-8501, Japan
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  • Toshio Terashima,

    1. Department of Anatomy, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Shinji Takada,

    1. Center for Molecular and Developmental Biology, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
    2. Kondoh Differentiation Signalling Project, ERATO (Exploratory Research for Advanced Technology) of Japan Science and Technology Corporation (JST), 14 Yoshida kawaramachi, Sakyo-ku, Kyoto 606-8305, Japan
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  • Hirohei Yamamura,

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Shizuo Akira,

    1. Department of Biochemistry, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8131, Japan
    2. CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST), Chiyoda-ku, Tokyo 102-0081, Japan
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  • Yasuhiro Minami

    1. Department of Biochemistry, Kobe University, School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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Yasuhiro Minami E-mail: minami@kobe-u.ac.jp

Abstract

Backgrounds

A mouse receptor tyrosine kinase (RTK), mRor2, which belongs to the Ror-family of RTKs consisting of at least two structurally related members, is primarily expressed in the heart and nervous system during mouse development. To elucidate the function of mRor2, we generated mice with a mutated mRor2 locus.

Results

Mice with a homozygous mutation in mRor2 died just after birth, exhibiting dwarfism, severe cyanosis, and short limbs and tails. Whole-mount in situ hybridization analysis showed that mRor2 was expressed in the branchial arches, heart and limb/tailbuds, in addition to the developing nervous system. The mutants had cardiac septal defects, mainly a ventricular septal defect. In addition, an examination of the skeletal systems revealed that the mutants had shorter limbs, vertebrae and facial structure, with a particular defect in their distal portions, and that almost no calcification was observed in their distal limbs. Histological examination showed abnormalities in the chondrocytes.

Conclusions

Our findings suggest that mRor2 plays essential roles in the development of the heart and in limb/tail formation, in particular cardiac septal formation and ossification of distal portions of limbs and tails.

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