Expression pattern of the orphan receptor LGR4/GPR48 gene in the mouse

Abstract

Leucine-rich G-protein-coupled Receptors (LGR) constitute a subfamily of receptors related to glycoprotein hormone receptors. Amongst them, LGR4, LGR5 and LGR6 form a cluster for which natural agonists are still unknown. By an extensive gene trapping approach, Leighton et al. (2001) obtained a mouse line in which the LGR4 gene is disrupted by a trap vector carrying two biological markers, beta-geo (a fusion between bacterial beta-galactosidase and neomycin phosphotransferase) and a placental alkaline phosphatase (PLAP). Due to perinatal lethality, characterization of adult mice homozygous for this insertion has been impaired. In the present study we have investigated LacZ and PLAP activity patterns in heterozygous mice as a marker for LGR4 natural expression at both macroscopic and histological levels. We present a detailed atlas of LGR4 expression, which displays very wide expression with particularly strong activity in cartilages, kidneys, reproductive tracts and nervous system cells.

Lgr4 Protein Deficiency Induces Ataxia-like Phenotype in Mice and Impairs Long Term Depression at Cerebellar Parallel Fiber-Purkinje Cell Synapses

“…In Lgr4 ϩ/Ϫ mice, a high level of ␤-galactosidase activity was detected in PCs and within some cell bodies of interneurons in the molecular layer (Fig. 1, A and B), which is consistent with a previous report (27). The PCs were identified by their large soma and characteristic morphology, and they were further confirmed by immunostaining with a specific PC marker, calbindin D28K (Fig.…”

“…Our previous studies have demonstrated that Lgr4 plays important roles in various organs, including eye (15), bone (22), blood (16,17), intestine (23), testis (24), mammary gland (25), and prostate (26). Although a previous report showed strong expression in neurons of many brain regions, especially in cerebellar PCs (27), the role of Lgr4 in the central nervous system has not been studied.…”

Leucine-Rich Repeat-Containing G-Protein Coupled Receptor 5/GPR49 Activates G12/13-Rho GTPase Pathway

“…LGR5 and LGR6 have attracted much attention from the stem cell community as a result of their specific expression in proliferating adult stem cells in various tissues, including hair follicles, intestines, stomach, and skin, whereas LGR4 shows a broader expression pattern that extends beyond stem cells (Barker and Clevers, 2010;Van Schoore et al, 2005). Furthermore, LGR4 and LGR5 null mice show neonatal lethality, whereas LGR6 knockout mice are healthy and fertile Morita et al, 2004;Snippert et al, 2010).…”

Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer

“…In contrast, Lgr4 expression is typically present on, but not restricted to, Lgr5/Lgr6 adult stem cell compartments in these tissues (for comprehensive review, see Barker and Clevers, 2010). Lgr6 KO mice are healthy and fertile, but both Lgr4 null and Lgr5 null mutations are neonatal-lethal, defining an essential role for Lgr4 and Lgr5 during embryogenesis (Mazerbourg et al, 2004;Van Schoore et al, 2005). However, their function on the stem cell compartments of adult tissues have only recently been investigated.…”