LGR4 is required for the cell survival of the peripheral mesenchyme at the embryonic stages of nephrogenesis.

In mice, homozygous Lgr4 inactivation results in hypoplastic kidneys. To understand better the role of LGR4 in kidney development, we performed an analysis of kidneys in Lgr4-/- embryos. We stained Lgr4-/- kidneys with anti-WT1 and anti-Cleaved Caspase3 antibodies at E16.

Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3.

We previously reported that Lgr4 has a critical role in the morphogenesis of kidney, but the detailed functions of Lgr4 in kidney development have not been elucidated. In contrast to Lgr4 null mice with 129Ola × C57BL/6J mixed background, C57BL/6J-backcrossed Lgr4 null mice (Lgr4(-/-)) showed the severe phenotype of embryonic lethality and also had dilated tubules in kidneys at E16.5.

Reduced fertility with impairment of early-stage embryos observed in mice lacking Lgr4 in epithelial tissues.

Lgr4 is one of the genes identified as novel G protein-coupled receptor genes designated Lgr4-Lgr8, with high homology with FSH receptor, LH receptor, and TSH receptor genes, but studies of Lgr4-mutant mice have suggested that Lgr4 has essential functions in development. This is the first report describing the relationship between the functions of Lgr4 and female reproductive systems.