AGE DEPENDENT REGULATION OF HEMOSTASIS

年龄依赖性止血调节

基本信息

  • 批准号:
    6011569
  • 负责人:
  • 金额:
    $ 33.28万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-07-01 至 2003-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: (Adapted from investigator's abstract) Blood coagulation activity in the normal human population elevates with advancing age. When combined with age-dependent disorders like atherosclerosis, this increase in the coagulation potential may play a role in the increased frequency of cardiovascular and thrombotic disorders in the elderly. Presently, little is known about the molecular mechanisms responsible for this phenomenon and homeostasis of the coagulation system in general. The long-term goal of this proposal is to determine the molecular mechanisms underlying age-dependent regulation and homeostasis of the blood coagulation system. The factor IX gene will serve as an initial model gene for intensive studies. Recently the applicant has identified two major activities associated with specific regions of the factor IX gene that are essential for age-dependent regulation of expression. This proposal has five specific aims. Specific Aim 1 is to establish the mechanisms of action of two cis-acting elements, AE5' (a PEA3 binding element) and AE3' (a sequence containing extensive dinucleotide repeats) in age-dependent regulation of the human factor IX gene. Specific Aim 2 is to delineate the switch mechanisms in expression of transcriptional factors over the puberty period. Specific Aim 3 is to identify potential additional gene structures with modifying activities on age-dependent regulation of the gene. Specific Aim 4 is to determine the physiological significance of advancing age-dependent elevation in factor IX gene expression by constructing a mouse model lacking such elevation in the endogenous mouse factor IX gene. Specific Aim 5 is to determine the biological significance of elevated or lowered plasma factor IX levels in relation to age. The molecular mechanisms established for the factor IX gene will facilitate subsequent studies on other key coagulation factors and regulators, laying the foundation for comprehensive understanding of the overall age-dependent regulation (homeostasis) of the coagulation system. Such knowledge may help develop novel and/or improved treatments for hemorrhagic disorders as well as thrombotic and cardiovascular diseases in the elderly.
描述:(改编自研究者摘要)血液凝固活性

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)

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KOTOKU KURACHI其他文献

KOTOKU KURACHI的其他文献

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{{ truncateString('KOTOKU KURACHI', 18)}}的其他基金

AGE DEPENDENT REGULATION OF HEMOSTASIS
年龄依赖性止血调节
  • 批准号:
    6185022
  • 财政年份:
    1999
  • 资助金额:
    $ 33.28万
  • 项目类别:
AGE DEPENDENT REGULATION OF HEMOSTASIS
年龄依赖性止血调节
  • 批准号:
    6390655
  • 财政年份:
    1999
  • 资助金额:
    $ 33.28万
  • 项目类别:
MOLECULAR BIOLOGY OF BLOOD COAGULATION FACTORS
凝血因子的分子生物学
  • 批准号:
    6244634
  • 财政年份:
    1997
  • 资助金额:
    $ 33.28万
  • 项目类别:
MOLECULAR BIOLOGY OF BLOOD COAGULATION FACTORS
凝血因子的分子生物学
  • 批准号:
    6274667
  • 财政年份:
    1997
  • 资助金额:
    $ 33.28万
  • 项目类别:
GENE THERAPY FOR HEMOPHILIA B
B 型血友病的基因治疗
  • 批准号:
    6052053
  • 财政年份:
    1994
  • 资助金额:
    $ 33.28万
  • 项目类别:
GENE THERAPY FOR HEMOPHILIA B
B 型血友病的基因治疗
  • 批准号:
    2029303
  • 财政年份:
    1994
  • 资助金额:
    $ 33.28万
  • 项目类别:
GENE THERAPY FOR HEMOPHILIA B
B 型血友病的基因治疗
  • 批准号:
    2771399
  • 财政年份:
    1994
  • 资助金额:
    $ 33.28万
  • 项目类别:
GENE THERAPY FOR HEMOPHILIA B
B 型血友病的基因治疗
  • 批准号:
    2519464
  • 财政年份:
    1994
  • 资助金额:
    $ 33.28万
  • 项目类别:
GENE THERAPY FOR HEMOPHILIA B
B 型血友病的基因治疗
  • 批准号:
    2231783
  • 财政年份:
    1994
  • 资助金额:
    $ 33.28万
  • 项目类别:
GENE THERAPY FOR HEMOPHILIA B
B 型血友病的基因治疗
  • 批准号:
    2231784
  • 财政年份:
    1994
  • 资助金额:
    $ 33.28万
  • 项目类别:

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