P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse. Academic Article uri icon


  • 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 proceedings

  • Genomics

author list (cited authors)

  • Zhang, Q., Qiu, P., Arreaza, M. G., Simon, J. S., Golovko, A., Laverty, M., ... Murgolo, N. J.

citation count

  • 16

complete list of authors

  • Zhang, Qing||Qiu, Ping||Arreaza, M Gladys||Simon, Jason S||Golovko, Andrei||Laverty, Maureen||Vassileva, Galya||Gustafson, Eric L||Rojas-Triana, Alberto||Bober, Loretta A||Hedrick, Joseph A||Monsma, Frederick J||Greene, Jonathan R||Bayne, Marvin L||Murgolo, Nicholas J

publication date

  • November 2007