Molecular and Cellular Biology, January 2004, p. 687-696, Vol. 24, No. 2
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.2.687-696.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Impaired Nipple Development and Parturition in LGR7 Knockout Mice
Magda A. M. Krajnc-Franken, Ad J. M. van Disseldorp, Jasper E. Koenders, Sietse Mosselman, Marcel van Duin, and Jan A. Gossen*
N.V. Organon, Department of Pharmacology, 5340 BH Oss, The Netherlands
Received 28 July 2003/
Returned for modification 30 September 2003/
Accepted 21 October 2003
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.
* Corresponding author. Mailing address: N.V. Organon, Department of Pharmacology, Molenstraat 110, P.O. Box 20, 5340 BH Oss, The Netherlands. Phone: 31-412-662283. Fax: 31-412-663532. E-mail: jan.gossen{at}organon.com.
Molecular and Cellular Biology, January 2004, p. 687-696, Vol. 24, No. 2
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.2.687-696.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.