P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse
P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse
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DOI：
10.1016/j.ygeno.2007.07.011
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发表时间：
2007-11-01
期刊：
影响因子：
4.4
通讯作者：
Murgolo, Nicholas J.
中科院分区：
文献类型：
--
作者：
Zhang, Qing;Qiu, Ping;Murgolo, Nicholas J.
缺乏GPR 103 A表达的小鼠显示骨质减少。对与骨密度相关的小鼠数量性状基因座文献的分析表明，GPR 103 A配体P518/Qrfp（染色体2 qB）是骨质疏松症的候选基因。对小鼠P518/Qtfp的启动子和编码区从基因组DNA进行测序，所述基因组DNA获自嗜肺吸虫病易感菌株SAMP 6和对照菌株SAMR 1、A/J、AKR/J、BALB/c、C3 H/HeJ、C57 BL/6 J和DBA/2.1。仅在SAMP 6基因组DNA中鉴定出四种单核苷酸多态性（SNP），即：1773 T -> C，g.110 A -> G（N37S），g.188 G -> A（ROK），和g.135 T -> C（H45 H）。启动子SNP产生了一个新的神经元限制性沉默因子结合位点，一种减少非神经元组织中基因表达的阻遏物。TaqMan分析表明，与SAMRI或C57 BL/6 J对照菌株相比，SAMP 6中的P518/Qrfp肝脏表达低五倍。人、小鼠和大鼠的组织分布显示P518/Qtfp及其受体在骨和脊髓中表达。P518/Qrfp功能在维持骨密度中的直接作用。(c)2007爱思唯尔公司All rights reserved.
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/Qtfp 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/2.1. Four sing I e-nucleotide polymorphisms (SNPs) were identified in only SAMP6 genomic DNA, g.-1773 T -> C, g.110 A -> G (N37S), g.188 G -> A (ROK), 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 SAMRI or C57BL/6J control strains. Tissue distribution of human, mouse, and rat P518/Qtfp and its receptors showed expression in bone and spinal cord. A direct role for P518/Qrfp function in maintaining bone mineral density is suggested. (c) 2007 Elsevier Inc. All rights reserved.