Deficiency of phospholipase C-γ1 impairs renal development and hematopoiesis

Author:

Shirane Masatoshi12,Sawa Hirofumi3,Kobayashi Yoshiyasu3,Nakano Toru4,Kitajima Kenji4,Shinkai Yoichi25,Nagashima Kazuo3,Negishi Izumi26

Affiliation:

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

Abstract

Phospholipase C-γ1 (PLC-γ1) is involved in a variety of intracellular signaling via many growth factor receptors and T-cell receptor. To explore the role of PLC-γ1 in vivo, we generated the PLC-γ1-deficient (plc-γ1–/–) mice, which died of growth retardation at embryonic day 8.5-9.5 in utero. Therefore, we examined plc-γ1–/– chimeric mice generated with plc-γ1–/– embryonic stem (ES) cells for further study. Pathologically, plc-γ1–/– 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-γ1–/– ES cells in the mutant chimeras. However, differentiation of plc-γ1–/– 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-γ1 plays an essential role in the renal development and hematopoiesis in vivo.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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