Conditional knockout of Lgr4 leads to impaired ductal elongation and branching morphogenesis in mouse mammary glands.

We have analyzed the function of LGR4 in the development of various mouse epithelial tissues. Here we first report the retarded invasion of mammary ducts into the fat pad observed in Lgr4(K5 KO) mice at 4 weeks, compared with that of age-matched Lgr4(K5 ctrl). Furthermore, we demonstrate a significant decrease in mammary ductal branching in Lgr4(K5 KO) at several stages (4, 6 and 8 weeks). On the other hand, immunohistochemical analysis of the mammary gland of Lgr4(K5 KO) using anti-αSMA, anti-K18 and anti-laminin antibodies showed structures similar to those of Lgr4(K5 ctrl) mammary glands. In addition, we did not detect significant differences in the expression of ERα, which was suggested to be a downstream molecule of LGR4, and Lgr4(K5 KO) showed no retarded invasion in the response to 17ß-estradiol administration. Furthermore, the phosphorylated form of Smad1/5/8 was normally detected in the mammary gland of Lgr4(K5 KO).