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P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse
Qing Zhang ,
Ping Qiu ,
M. Gladys Arreaza ,
Jason S. Simon ,
Andrei Golovko ,
Maureen Laverty ,
Galya Vassileva ,
Eric L. Gustafson ,
Alberto Rojas-Triana ,
Loretta A. Bober ,
Joseph A. Hedrick ,
Frederick J. Monsma ,
Jonathan R. Greene ,
Marvin L. Bayne ,
Nicholas J. Murgolo
November 2007
November 2007
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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.