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Identification of quantitative trait loci specifying the onset of osteoporosis using a murine model.

使用小鼠模型鉴定指定骨质疏松症发作的数量性状基因座。

基本信息

批准号：
09470316
负责人：
TSUBOYAMA Tadao
金额：
$ 8.26万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470316/
关键词：
Osteoporosis Animal model Genetic Background QTL analysis

项目摘要

The whole genome scan for quantitative trait loci (QTLs) specifying peak bone mass was performed with the F2 intercrosses of SAMP6, an established murine model of senile osteoporosis exhibiting a significantly lower peak bone mass, and SAMP2, exhibitinga higher peak bone mass. The bone masses of mice femurs were assayed photometrically using microdensitometry in 488 F2 progeny at 4 months of age, when the animals were reaching peak bone mass. Genetic markers were typed at 90 loci spanning all chromosomes except the Y.By interval mapping of 246 male F2 mice, two loci were identified with significant linkage to peak bone mass, one on chromosome 11 with a maximum lod score of 10.8 (22.2% of the total variance), and another on chromosome 13 with a maximum lod score of 5.8 (10.0%). Another locus on the X chromosome was suggestive of a QTL, We found no differences between SAMP6 and SAMP2 by sequencing genomic regions of G-CSF and a part of cDNA of chondroadherinin, which are candidate genes influencing low peak bone mass. We are constructing interval-specific congenic mice carrying appropriate SAMP6 and SAMP2 regions in order to refine the genetic locations of these QTLs. By cross-mating each congenic strain with parental strains and finding out the progenies that have a recombination within the putative QTL region detected in this study, it will be possible to make a high-resolution map and contract the QTL region. At present, we have established each N7 generation and homozygous mice by intercross-mating the N7 miceon Chr. 11, 13 and the X.These findings should be useful to elucidate the genetics of osteoporosis.

本研究采用老年性骨质疏松症小鼠模型SAMP 6和SAMP 2杂交F2，对峰值骨量进行了全基因组扫描，以确定峰值骨量的数量性状位点（QTL）。使用显微密度测定法对488只4月龄F2子代小鼠股骨的骨量进行光度测定，此时动物达到峰值骨量。通过对246只雄性F2小鼠的间隔作图，确定了两个与峰值骨量具有显著连锁的基因座，一个在11号染色体上，最大lod得分为10.8（总方差的22.2%），另一个在13号染色体上，最大lod得分为5.8（10.0%）。X染色体上的另一个位点提示了一个QTL，我们通过对影响低峰值骨量的候选基因G-CSF和软骨粘附素的部分cDNA的基因组区域进行测序，发现SAMP 6和SAMP 2之间没有差异。我们正在构建携带适当SAMP 6和SAMP 2区域的间隔特异性同源小鼠，以细化这些QTL的遗传位置。通过将每个同源株系与亲本株系杂交，找出在本研究中检测到的推定QTL区域内发生重组的后代，将有可能制作高分辨率的图谱并缩小QTL区域。目前，我们已经建立了每个N7代和纯合子小鼠，通过交叉交配的N7小鼠Chr. 11，13和X。这些发现将有助于阐明骨质疏松症的遗传学。