This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mazerbourg, S. Articles by Hsueh, A. J. W. Search for Related Content PubMed PubMed Citation Articles by Mazerbourg, S. Articles by Hsueh, A. J. W.

Leucine-Rich Repeat-Containing, G Protein-Coupled Receptor 4 Null Mice Exhibit Intrauterine Growth Retardation Associated with Embryonic and Perinatal Lethality

Division of Reproductive Biology, Department of Obstetrics and Gynecology (S.M., S.S., C.A.K., J.V.Z, K.K., A.J.W.H.) and Departments of Comparative Medicine (D.M.B.), and Biology (L.V.G, H.R., M.T.-L.), Stanford University, Stanford, California 94305

Address all correspondence and requests for reprints to: Aaron J. W. Hsueh, Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317. E-mail: aaron.hsueh{at}stanford.edu.

Leucine-rich repeat-containing, G protein-coupled receptors (LGRs) belong to the largest mammalian superfamily of proteins with seven-transmembrane domains. LGRs can be divided into three subgroups based on their unique domain arrangement. Although two subgroups have been found to be receptors for glycoprotein hormones and relaxin-related ligands, respectively, the third LGR subgroup, consisting of LGR4–6, are orphan receptors with unknown physiological roles. To elucidate the functions of this subgroup of LGRs, LGR4 null mice were generated using a secretory trap approach to delete the majority of the LGR4 gene after the insertion of a ß-galactosidase reporter gene immediately after exon 1. Tissues expressing LGR4 were analyzed based on histochemical staining of the transgene driven by the endogenous LGR4 promoter. LGR4 was widely expressed in kidney, adrenal gland, stomach, intestine, heart, bone/cartilage, and other tissues. The expression of LGR4 in these tissues was further confirmed by immunohistochemical studies in wild-type animals. Analysis of the viability of 250 newborn animals suggested a skewed inheritance pattern, indicating that only 40% of the expected LGR4 null mice were born. For the LGR4 null mice viable at birth, most of them died within 2 d. Furthermore, the LGR4 null mice showed intrauterine growth retardation as reflected by a 14% decrease in body weight at birth, together with 30% and 40% decreases in kidney and liver weights, respectively. The present findings demonstrate the widespread expression of LGR4, and an essential role of LGR4 for embryonic growth, as well as kidney and liver development. The observed pre- and postnatal lethality of LGR4 null mice illustrates the importance of the LGR4 signaling system for the survival and growth of animals during the perinatal stage.

This article has been cited by other articles:

				H. Song, J. Luo, W. Luo, J. Weng, Z. Wang, B. Li, D. Li, and M. Liu Inactivation of G-protein-coupled Receptor 48 (Gpr48/Lgr4) Impairs Definitive Erythropoiesis at Midgestation through Down-regulation of the ATF4 Signaling Pathway J. Biol. Chem., December 26, 2008; 283(52): 36687 - 36697. [Abstract] [Full Text] [PDF]

				C. Jin, F. Yin, M. Lin, H. Li, Z. Wang, J. Weng, M. Liu, X. Da Dong, J. Qu, and L. Tu GPR48 Regulates Epithelial Cell Proliferation and Migration by Activating EGFR during Eyelid Development Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4245 - 4253. [Abstract] [Full Text] [PDF]

				J. Weng, J. Luo, X. Cheng, C. Jin, X. Zhou, J. Qu, L. Tu, D. Ai, D. Li, J. Wang, et al. Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2 PNAS, April 22, 2008; 105(16): 6081 - 6086. [Abstract] [Full Text] [PDF]

				T. Hoshii, T. Takeo, N. Nakagata, M. Takeya, K. Araki, and K.-i. Yamamura LGR4 Regulates the Postnatal Development and Integrity of Male Reproductive Tracts in Mice Biol Reprod, February 1, 2007; 76(2): 303 - 313. [Abstract] [Full Text] [PDF]

				Y. Gao, K. Kitagawa, Y. Hiramatsu, H. Kikuchi, T. Isobe, M. Shimada, C. Uchida, T. Hattori, T. Oda, K. Nakayama, et al. Up-regulation of GPR48 Induced by Down-regulation of p27Kip1 Enhances Carcinoma Cell Invasiveness and Metastasis Cancer Res., December 15, 2006; 66(24): 11623 - 11631. [Abstract] [Full Text] [PDF]

				A J W Hsueh, P Bouchard, and I Ben-Shlomo Hormonology: a genomic perspective on hormonal research J. Endocrinol., December 1, 2005; 187(3): 333 - 338. [Abstract] [Full Text] [PDF]

				C.-W. Luo, E. M. Dewey, S. Sudo, J. Ewer, S. Y. Hsu, H.-W. Honegger, and A. J. W. Hsueh Bursicon, the insect cuticle-hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2 PNAS, February 22, 2005; 102(8): 2820 - 2825. [Abstract] [Full Text] [PDF]