Embryonic cardiomyocyte hypoplasia and craniofacial defects in Gαq/Gα11-mutant mice
Embryonic cardiomyocyte hypoplasia and craniofacial defects in Gαq/Gα11-mutant mice
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DOI：
10.1093/emboj/17.15.4304
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发表时间：
1998-08-03
期刊：
影响因子：
11.4
通讯作者：
Wilkie, TM
中科院分区：
文献类型：
--
作者：
Offermanns, S;Zhao, LP;Wilkie, TM
G(q)类异三聚体G蛋白与生理和病理条件下调节心脏生长的信号通路有关。在广泛表达的G α (q)类基因G α (q)和G α(11)（,）中携带失活突变的敲除小鼠表明，这些基因中至少有两个活性等位基因是维持子宫外生命所必需的。只携带一个完整等位基因的小鼠[G α (q)((-/+))；G alpha(11)（(-/-)）或G alpha(q)((-/-))；G α(11)((-/+))]在出生后不久死亡。这些突变体显示出高发生率的心脏畸形。另外，G α (q)((-/-))；G α(11)（(-/+)）新生儿出现颅面缺损。缺失G α (q)和G α (11) [G α (q)((-/-))]的小鼠；G α(11)((-/-))]在胚胎第11天因心肌细胞发育不全而死亡，这些数据表明G α (q)和G α(11)基因功能重叠，表明G(q)类G蛋白在心脏生长发育中起关键作用。
Heterotrimeric G proteins of the G(q) class have been implicated in signaling pathways regulating cardiac growth under physiological and pathological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed G alpha(q) class genes, G alpha(q) and G alpha(11)(,) demonstrate that at least two active alleles of these genes are required for extrauterine life. Mice carrying only one intact allele [G alpha(q)((-/+)); G alpha(11)((-/-)) or G alpha(q)((-/-)); G alpha(11)((-/+))] died shortly after birth. These mutants showed a high incidence of cardiac malformation. In addition, G alpha(q)((-/-)); G alpha(11)((-/+)) newborns suffered from craniofacial defects. Mice lacking both G alpha(q) and G alpha(11) [G alpha(q)((-/-)); G alpha(11)((-/-))] died at embryonic day 11 due to cardiomyocyte hypoplasia, These data demonstrate overlap in G alpha(q) and G alpha(11) gene functions and indicate that the G(q) class of G proteins plays a crucial role in cardiac growth and development.