title: P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse.
abstract: Mice lacking GPR103A expression display osteopenia. Analysis of mouse quantitative trait loci literature associated with bone mineral density suggested GPR103A ligand P518/Qrfp (chromosome 2qB) as a candidate osteoporosis gene. Promoter and coding regions of mouse P518/Qrfp were sequenced from genomic DNA obtained from the osteoporosis-prone strain SAMP6 and control strains SAMR1, A/J, AKR/J, BALB/c, C3H/HeJ, C57BL/6J, and DBA/2J. Four single-nucleotide polymorphisms (SNPs) were identified in only SAMP6 genomic DNA, g.-1773 T-->C, g.110 A-->G (N37S), g.188 G-->A (R63K), and g.135 T-->C (H45H). The promoter SNP generated a novel neuron-restrictive silencing factor binding site, a repressor that decreases gene expression in nonneuronal tissues. TaqMan analysis demonstrated fivefold lower P518/Qrfp liver expression in SAMP6 versus SAMR1 or C57BL/6J control strains. Tissue distribution of human, mouse, and rat P518/Qrfp and its receptors showed expression in bone and spinal cord. A direct role for P518/Qrfp function in maintaining bone mineral density is suggested.
authors.affiliation: Department of Discovery Technologies, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: M Gladys
authors.initials: MG
authors.lastname: Arreaza
authors.forename: Jason S
authors.initials: JS
authors.lastname: Simon
authors.forename: Andrei
authors.initials: A
authors.lastname: Golovko
authors.forename: Maureen
authors.initials: M
authors.lastname: Laverty
authors.forename: Galya
authors.initials: G
authors.lastname: Vassileva
authors.forename: Eric L
authors.initials: EL
authors.lastname: Gustafson
authors.forename: Alberto
authors.initials: A
authors.lastname: Rojas-Triana
authors.forename: Loretta A
authors.initials: LA
authors.lastname: Bober
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hedrick
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Monsma
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Greene
authors.forename: Marvin L
authors.initials: ML
authors.lastname: Bayne
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Murgolo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D010455:Peptides; C511787:QRFP peptide; C476583:Qrfpr protein, mouse; D043562:Receptors, G-Protein-Coupled