Deficiency of phospholipase C-gamma1 impairs renal development and hematopoiesis.
Phospholipase C-gamma1 (PLC-gamma1) is involved in a variety of intracellular signaling via many growth factor receptors and T-cell receptor. To explore the role of PLC-gamma1 in vivo, we generated the PLC-gamma1-deficient (plc-gamma1(-/-)) mice, which died of growth retardation at embryonic day 8.5-9.5 in utero. Therefore, we examined plc-gamma1(-/-) chimeric mice generated with plc-gamma1(-/-) embryonic stem (ES) cells for further study. Pathologically, plc-gamma1(-/-) 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-gamma1(-/-) ES cells in the mutant chimeras. However, differentiation of plc-gamma1(-/-) 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-gamma1 plays an essential role in the renal development and hematopoiesis in vivo.
Shirane
M
M
Department of Product Research and. Department of Molecular Oncology, Nippon Roche Research Center, Kajiwara 200, Kamakura, Kanagawa 247-8530, Japan.
Sawa
H
H
Kobayashi
Y
Y
Nakano
T
T
Kitajima
K
K
Shinkai
Y
Y
Nagashima
K
K
Negishi
I
I
D000818:Animals; D015703:Antigens, CD / Q000302:isolation & purification; D002454:Cell Differentiation; D002678:Chimera; D004622:Embryo, Mammalian / Q000166:cytology; D006410:Hematopoiesis / Q000235:genetics*; D006413:Hematopoietic System / Q000002:abnormalities; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics; D008221:Lymphoid Tissue / Q000002:abnormalities; D051379:Mice; D008817:Mice, Mutant Strains; D021782:Multicystic Dysplastic Kidney / Q000209:etiology* / Q000235:genetics; D051966:Phospholipase C gamma; D000071176:Signaling Lymphocytic Activation Molecule Family; D013234:Stem Cells / Q000166:cytology; D010738:Type C Phospholipases / Q000172:deficiency* / Q000235:genetics
D015703:Antigens, CD; D007527:Isoenzymes; C498972:Ly9 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family; D010738:Type C Phospholipases; D051966:Phospholipase C gamma