title: Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice.
abstract: 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.
authors.affiliation: N.V. Organon, part of Schering-Plough Corporation, Target Discovery, Molenstraat 110, 5340 BH Oss, The Netherlands.
authors.forename: Han
authors.initials: H
authors.lastname: Gerrits
authors.forename: Dorette S
authors.initials: DS
authors.lastname: van Ingen Schenau
authors.forename: Nicole E C
authors.initials: NE
authors.lastname: Bakker
authors.forename: Ad J M
authors.initials: AJ
authors.lastname: van Disseldorp
authors.forename: Ankie
authors.initials: A
authors.lastname: Strik
authors.forename: Laura S
authors.initials: LS
authors.lastname: Hermens
authors.forename: Tim B
authors.initials: TB
authors.lastname: Koenen
authors.forename: Magda A M
authors.initials: MA
authors.lastname: Krajnc-Franken
authors.forename: Jan A
authors.initials: JA
authors.lastname: Gossen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000196:embryology; D018376:Cardiovascular Abnormalities / Q000235:genetics* / Q000401:mortality*; D002319:Cardiovascular System / Q000196:embryology; D005260:Female; D018014:Gene Transfer Techniques; D005804:Genes, Lethal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D054387:Receptors, CXCR; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics*
chemical_list: C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR; D043562:Receptors, G-Protein-Coupled