Leucine-rich repeat-containing g protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice
Leucine-rich repeat-containing g protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice
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DOI：
10.1159/000093999
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Nishimori, Katsuhiko
中科院分区：
文献类型：
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作者：
Kato, Shigeki;Matsubara, Mitsunobu;Nishimori, Katsuhiko
富含亮氨酸重复序列的G蛋白偶联受体(LGR)-4是一种具有七跨膜结构域的G蛋白偶联受体（GPCR）。ILGRs在进化和结构上是系统发育的，分为三个亚群，是所谓的孤儿受体的成员，其配体尚未确定。我们通过靶向缺失Lgr4 （Gpr48）的部分外显子18产生了缺失Lgr4 （Gpr48）的敲除小鼠，该外显子18编码受体的跨膜和信号转导结构域。Lgr4缺失小鼠的出生频率远低于Lgr4杂合小鼠（Lgr4(+/-)）杂交的25%的预期频率。在子宫内存活的Lgr4缺失小鼠几乎都在出生后不久死亡。我们观察到小鼠肾发育不全，血浆肌酐浓度升高。PO阴性小鼠肾脏的组织学分析显示肾小球的总数和密度明显减少。因此，Lgr4的功能对调节小鼠肾脏发育至关重要。本研究提示Lgr4基因是LGRs中一个新的重要成员，参与了一组与肾脏遗传性疾病有关的基因。版权所有(c) 2006 S. Karger AG，巴塞尔。
Leucine-rich repeat-containing G protein-coupled receptor (LGR)-4 is a G protein-coupled receptor (GPCR) with a seven-transmembrane domain structure. ILGRs are evolutionally and structurally phylogenetic, classified into three subgroups and are members of the so-called orphan receptors whose ligands have yet to be identified. We generated knockout mice lacking Lgr4 (Gpr48) by targeted deletion of part of exon 18, which codes for the transmembrane and signal-transducing domains of the receptor. Lgr4 null mice were born at much less than the 25% expected frequency from crosses of Lgr4 heterozygous mice (Lgr4(+/-)). Lgr4 null mice that survived in utero died shortly after birth in almost all cases. We observed striking renal hypoplasia in the null mice, accompanied by elevated concentration of plasma creatinine. Histological analysis of the PO null mouse kidney showed a notable decrease in the total number and density of the glomerulus. Thus, the function of Lgr4 is essential to regulate renal development in the mouse. This study suggests that the Lgr4 gene is a new and important member of LGRs involved in a group of genes responsible for hereditary disease in the kidney. Copyright (c) 2006 S. Karger AG, Basel.