MOLECULAR GENETICS OF OSTEOPENIA IN THE SENESCENCE ACCELERATED MOUSE

加速衰老小鼠骨质减少的分子遗传学

基本信息

  • 批准号:
    6234608
  • 负责人:
  • 金额:
    $ 16.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1997
  • 资助国家:
    美国
  • 起止时间:
    1997-06-01 至 1998-05-31
  • 项目状态:
    已结题

项目摘要

Bone density is a highly heritable quantitative trait in humans, declines markedly with senescence, and is the major determinant of skeletal fragility in osteoporosis. The SAM/P-6 mouse displays an early-onset osteopenic phenotype featuring diminished peak bone mineral density, declining further after maturity, and markedly decreased numbers of osteoblast progenitors in bone marrow. This progressive osteopenia is also highly heritable, with about 60% of the variation in bone density in interstrain cross progeny attributable to genetic factors. It is proposed to identify genetic loci contributing to osteopenia and associated parameters, by standard gene-mapping procedures developed for quantitative trait loci, coupled to an improved technique for assessing bone mineral density in vivo. Crosses will be constructed between SAM/P-6 and a control line with normal-bone-density, SAM/R-1. The polygenic basis of osteopenia in P-6 mice, and the extent of its heritability, will be assessed for several indices of normal osteogenesis. Microsatellite- repeat markers which distinguish between the P-6 and R-1 genomes will be used to localize genes contributing to osteopenia, by maximum-likelihood analysis of genotype and bone-density data for the genetically variable F(2) progeny of a P-6 times R-1 cross. If several quantitative trait loci are identified which correlate with bone density, they will be tested for interactions in generating osteopenia. Endogenous retroviral integration sites will be probed to determine whether any co-localize with osteopenia loci, implying insertional mutation of the implicated genes and enabling their rapid isolation. To test the roles of individual osteopenia loci, and to allow their high-resolution mapping, congenic lines will be constructed which contain such loci in the genetic background of the contrasting-phenotype parent. Limited back-crossing strategies, and congenic strains based on tracking osteopenia-associated phenotypes and genotypes at the implicated loci, will also be employed to facilitate detailed mapping. The regions thus identified will be analyzed for previously-implicated "candidate genes" and for sequence identity to transcripts in a cDNA library prepared from bone marrow cells. Aided by high-density genetic maps being constructed for human and mouse genomes, which are largely congruent, localization of osteopenia genes in SAMP/P-6 mice should expedite the search for human genes underlying osteoporosis.
骨密度是人类高度遗传的数量性状, 与衰老明显,是骨骼的主要决定因素, 骨质疏松症的脆弱性 SAM/P-6小鼠表现出早发性 骨质减少表型特征在于峰值骨矿物质密度降低, 成熟后进一步下降, 骨髓中的成骨祖细胞。 这种进行性骨质减少 也是高度遗传的,大约60%的骨密度变化, 可归因于遗传因素的品系间杂交后代。 拟 以确定导致骨质减少的遗传位点和相关的 参数,通过标准基因定位程序开发的定量 性状基因座,结合评估骨矿物质的改进技术 体内密度。 将在SAM/P-6和 正常骨密度对照线,SAM/R-1。 多基因基础 P-6小鼠的骨量减少及其遗传性程度将被 评估正常骨生成的几个指标。 微卫星- 区分P-6和R-1基因组的重复标记将被 用于通过最大似然法定位导致骨质减少的基因 分析遗传变量的基因型和骨密度数据 F(2)P-6 × R-1杂交的后代。 如果几个数量性状基因座 与骨密度相关,将对其进行检测, 相互作用产生骨质疏松症。 内源性逆转录病毒整合 将探测部位,以确定是否有任何骨质减少共定位 基因座,这意味着相关基因的插入突变, 快速隔离。 为了测试个体骨质减少位点的作用, 并允许他们的高分辨率映射,同源系将 构建的基因座,其在所述基因的遗传背景中含有这样的基因座, 对照表型亲本 有限的回交策略,以及 基于追踪骨质减少相关表型的同类菌株, 还将采用在所涉及的基因座处的基因型来促进 详细地图 将分析由此确定的区域, 先前涉及的“候选基因”,并且对于序列同一性, 在从骨髓细胞制备的cDNA文库中的转录本。 援建 人类和小鼠基因组的高密度遗传图谱正在构建中, 这在很大程度上是一致的,SAMP/P-6中骨质减少基因的定位 老鼠应该加快寻找人类骨质疏松症的基因。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

ROBERT S REIS其他文献

ROBERT S REIS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('ROBERT S REIS', 18)}}的其他基金

MOLECULAR GENETICS OF OSTEOPENIA IN THE SENESCENCE ACCELERATED MOUSE
加速衰老小鼠骨质减少的分子遗传学
  • 批准号:
    6316956
  • 财政年份:
    2000
  • 资助金额:
    $ 16.7万
  • 项目类别:
MOLECULAR GENETICS OF OSTEOPENIA IN THE SENESCENCE ACCELERATED MOUSE
加速衰老小鼠骨质减少的分子遗传学
  • 批准号:
    6098703
  • 财政年份:
    1999
  • 资助金额:
    $ 16.7万
  • 项目类别:
MOLECULAR GENETICS OF OSTEOPENIA IN THE SENESCENCE ACCELERATED MOUSE
加速衰老小鼠骨质减少的分子遗传学
  • 批准号:
    6267687
  • 财政年份:
    1998
  • 资助金额:
    $ 16.7万
  • 项目类别:
MOLECULAR GENETICS OF OSTEOPENIA IN THE SENESCENCE ACCELERATED MOUSE
加速衰老小鼠骨质减少的分子遗传学
  • 批准号:
    6295644
  • 财政年份:
    1998
  • 资助金额:
    $ 16.7万
  • 项目类别:
MOLECULAR GENETICS OF OSTEOPENIA IN THE SENESCENCE ACCELERATED MOUSE
加速衰老小鼠骨质减少的分子遗传学
  • 批准号:
    5205067
  • 财政年份:
  • 资助金额:
    $ 16.7万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了