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Development 128, 5173-5180 (2001)
© 2001 The Company of Biologists Limited

DEVELOPMENT AND DISEASE

Deficiency of phospholipase C-{gamma}1 impairs renal development and hematopoiesis

Masatoshi Shirane1,2, Hirofumi Sawa3, Yoshiyasu Kobayashi3, Toru Nakano4, Kenji Kitajima4, Yoichi Shinkai2,5, Kazuo Nagashima3 and Izumi Negishi2,6,*

1 Department of Product Research and
2 Department of Molecular Oncology, Nippon Roche Research Center, Kajiwara 200, Kamakura, Kanagawa 247-8530, Japan
3 Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, CREST, JST, N15W7, Kita-Ku, Sapporo 060-8638, Japan
4 Department of Molecular Cell Biology, Osaka University Research Institute for Microbial Diseases, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan
5 Department of Cell Biology, Institute for Virus Research, Kyoto University, Seigoinkawara-machi 53, Sakyo-Ku, Kyoto 606-8507, Japan
6 Department of Dermatology, Gunma University School of Medicine, Showa-machi 3-39-22, Maebashi, Gunma 371-8511, Japan

*Author for correspondence at address 6 (e-mail: inegishi{at}showa.gunma-u.ac.jp)

Accepted October 9, 2001

Phospholipase C-{gamma}1 (PLC-{gamma}1) is involved in a variety of intracellular signaling via many growth factor receptors and T-cell receptor. To explore the role of PLC-{gamma}1 in vivo, we generated the PLC-{gamma}1-deficient (plc-{gamma}1–/–) mice, which died of growth retardation at embryonic day 8.5-9.5 in utero. Therefore, we examined plc-{gamma}1–/– chimeric mice generated with plc-{gamma}1–/– embryonic stem (ES) cells for further study. Pathologically, plc-{gamma}1–/– chimeras showed multicystic kidney due to severe renal dysplasia and renal tube dilation. Flow cytometric analysis and glucose phosphate isomerase assay revealed very few hematopoietic cells derived from the plc-{gamma}1–/– ES cells in the mutant chimeras. However, differentiation of plc-{gamma}1–/– ES cells into erythrocytes and monocytes/macrophages in vitro was observed to a lesser extent compared with control wild-type ES cells. These data suggest that PLC-{gamma}1 plays an essential role in the renal development and hematopoiesis in vivo.

Key words: PLC-{gamma}1, Chimeric mice, Renal dysplasia, Hematopoiesis, In vitro differentiation




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© The Company of Biologists Ltd 2001