LGR7 is a G-protein coupled receptor with structural homology to the gonadotrophin and thyrotrophin receptors. Recently, LGR7 was deorphanized, and it was shown that relaxin is the ligand for LGR7. To further study the function of this receptor, mice deficient for LGR7 were generated by replacing part of the transmembrane-encoding region with a LacZ reporter cassette. Here we show that LGR7 is expressed in various tissues, including the uterus, heart, brain, and testis. Fertility studies using female LGR7 ؊/؊ mice showed normal fertility and litter size. However, some females were incapable of delivering their pups, and several pups were found dead. Moreover, all offspring died within 24 to 48 h after delivery because female LGR7 ؊/؊ mice were unable to feed their offspring due to impaired nipple development. In some male LGR7 ؊/؊ mice, spermatogenesis was impaired, leading to azoospermia and a reduction in fertility. Interestingly, these phenomena were absent in mutant mice at older ages or in later generations. Taken together, results from LGR7 knockout mice indicate an essential role for the LGR7 receptor in nipple development during pregnancy. Moreover, a defect in parturition was observed, suggesting a role for LGR7 in the process of cervical ripening.LGR7 is a leucine-rich repeat-containing G-protein coupled receptor that was identified on the basis of its structural homology to the follicle-stimulating hormone, luteinizing hormone, and thyrotropin receptor family (4, 5). An interesting feature of these receptors are their large extracellular domains with leucine-rich repeats, which are commonly found in proteins involved in protein-protein interactions (8). Recently, LGR7 has been deorphanized, and it was shown that relaxin is the high-affinity ligand (6). The relaxin hormone has been studied in detail over the last few decades and has been implicated in many physiological processes related to the female reproductive system, including the induction of collagen remodeling and softening of the tissues of the birth canal prior to delivery. Also, the inhibition of uterine contractile activity and development of growth and differentiation of the mammary gland have been reported (2). In addition, relaxin has been implicated to trigger blood vessel dilatation in several organs and tissues, such as rat and mouse uterine endometrium and myometrium and mammary glands. Moreover, it has been shown that relaxin increases coronary flow, an effect which was paralleled by an increase of the production of nitric oxide, a potent vasodilatory agent (15).The observation that mice deficient for relaxin are unable to deliver milk to their pups due to impaired mammary gland development and the absence of nipple enlargement at the end of pregnancy has provided the first evidence for the function of relaxin. Moreover, it was reported that some of the mice were unable to deliver, most probably due to the absence of cervical softening or contractile activity (20). Phenotypic data related to the role of relaxin cardiac function indi...

CXCR7 is a G-protein coupled receptor that was recently deorphanized and shown to have SDF1 and I-TAC as high affinity ligands. Here we describe the characterization of CXCR7-deficient mice that were generated to further investigate the function of this receptor in vivo. Expression analysis using a LacZ reporter knockin revealed that postnatally Cxcr7 was specifically expressed in cardiomyocytes, vascular endothelial cells of the lung and heart, the cerebral cortex and in osteocytes of the bone. Adult tissues revealed high expression in cardiomyocytes and osteocytes. The observation that 70% of the Cxcr7-/- mice died in the first week after birth coincides with expression of Cxcr7 in vascular endothelial cells and in cardiomyocytes. An important role of CXCR7 in the cardiovascular system was further supported by the observation that hearts of the Cxcr7-/- mice were enlarged, showed myocardial degeneration and fibrosis of postnatal origin, and hyperplasia of embryonic origin. Despite high expression in osteocytes no apparent bone phenotype was observed, neither in combination with ovariectomy nor orchidectomy. Thus as CXCR7 does not seem to play an important role in bone our data indicate an important function of CXCR7 in the cardiovascular system during multiple steps of development.