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Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in mice

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Abstract

Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens, which act as its endogenous ligand. DDR2 regulates cell proliferation, cell adhesion, migration, extracellular matrix remodeling and reproductive functions. Both DDR2 null allele mice and mice with a recessive, loss-of-function allele for Ddr2 exhibit dwarfing and a reduction in body weight. However, the detailed mechanisms by which DDR2 exerts its positive systemic regulation of whole body size, local skeletal size and fat tissue volume remain to be clarified. To investigate the systemic role of DDR2 in body size regulation, we produced transgenic mice in which the DDR2 protein is overexpressed, then screened the transgenic mice for abnormalities using systematic mouse abnormality screening. The modified-SHIPRA screen revealed that only the parameter of body size was significantly different among the genotypes. We also discovered that the body length was significantly increased, while the body weight was significantly decreased in transgenic mice compared to their littermate controls. We also found that the epididymal fat pads were significantly decreased in transgenic mice compared to normal littermate mice, which may have been the cause of the leptin decrement in the transgenic mice. The new insight that DDR2 might promote metabolism in adipocyte cells is very interesting, but more experiments will be needed to elucidate the direct relation between DDR2 and adipose-derived hormones. Taken together, our data demonstrated that DDR2 might play a systemic role in the regulation of body size thorough skeletal formation and fat metabolism.

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Acknowledgments

This research was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; by the Morinaga Foundation; and by the Foundation for Growth Science.

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Authors and Affiliations

  1. Laboratory of Applied Genetics, Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo, 113-8657, Japan

    Ikuma Kawai, Hirokazu Matsumura, Wataru Fujii & Kunihiko Naito

  2. Laboratory of Veterinary Anatomy, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, 753-8515, Japan

    Ken Kusakabe, Yasuo Kiso & Kiyoshi Kano

  3. Laboratory of Developmental Biology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, 753-8515, Japan

    Kiyoshi Kano

  4. Biomedical Science Center for Translational Research (BSCTR), The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, 753-8515, Japan

    Kiyoshi Kano

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  1. Ikuma Kawai
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  2. Hirokazu Matsumura
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  3. Wataru Fujii
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  4. Kunihiko Naito
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  5. Ken Kusakabe
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  6. Yasuo Kiso
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  7. Kiyoshi Kano
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Correspondence to Kiyoshi Kano.

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Kawai, I., Matsumura, H., Fujii, W. et al. Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in mice. Transgenic Res 23, 165–175 (2014). https://doi.org/10.1007/s11248-013-9751-2

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  • DOI: https://doi.org/10.1007/s11248-013-9751-2

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