1. P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse.
- Author
-
Zhang Q, Qiu P, Arreaza MG, Simon JS, Golovko A, Laverty M, Vassileva G, Gustafson EL, Rojas-Triana A, Bober LA, Hedrick JA, Monsma FJ Jr, Greene JR, Bayne ML, and Murgolo NJ
- Subjects
- Amino Acid Sequence, Animals, Bone Density, Humans, Intercellular Signaling Peptides and Proteins, Ligands, Mice, Mice, Inbred Strains, Molecular Sequence Data, Rats, Sequence Homology, Amino Acid, Tissue Distribution, Bone Diseases, Metabolic genetics, Open Reading Frames genetics, Peptides genetics, Polymorphism, Single Nucleotide genetics, Promoter Regions, Genetic genetics, Quantitative Trait, Heritable, Receptors, G-Protein-Coupled genetics
- 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.
- Published
- 2007
- Full Text
- View/download PDF