AGING AND ANDROGEN RECEPTOR GENE REGULATION

衰老与雄激素受体基因调控

基本信息

  • 批准号:
    3122373
  • 负责人:
  • 金额:
    $ 16.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1993
  • 资助国家:
    美国
  • 起止时间:
    1993-01-01 至 1997-12-31
  • 项目状态:
    已结题

项目摘要

During the life-span of the rat, the liver of both male and female animals goes through three phases of androgen responsiveness, i.e., prepubertal ( <40 days) androgen-insensitivity, an androgen responsive phase of young-adulthood and androgen-insensitivity of senescence ( <750 days). These age-dependent changes in androgen sensitivity are correlated with the hepatic expression of the androgen receptor (AR) mRNA. Because of such a marked alteration in the expression of AR gene during the three periods of life, the rat liver offers a unique model for exploring the molecular mechanism of the temporal regulation of this gene. Such an age-dependent regulation of this receptor gene may be mediated through a programmed alteration of DNA-protein interactions that are critical for transcription. This proposal is designed to undertake a systematic analysis of DNA-protein interactions that are involved in the regulation of AR gene expression in the liver. In order to achieve this goal, the upstream regulatory region of the AR gene will be cloned and characterized. Fragments of the cloned gene will be used to identify specific protein-binding regions by DNase I in vitro foot-printing analysis. Age-specific alterations of DNA-binding nuclear factors will be subsequently characterized by band-shift analysis of labeled oligonucleotide duplexes corresponding to the foot-print regions of the AR gene. Cellular existence of DNA-protein interactions will be substantiated by in vivo foot-printing of primary heptocytes and DNase I hypersensitivity analysis of isolated liver nuclei. Once the age- specific DNA-protein interactions are characterized, their functional relevance will be substantiated by transfection assay of the wild type and appropriate mutant of the AR gene promoters ligated to heterologous reporter genes. The biological role of these interactions will be further authenticated by examining the specific requirements of the cis/trans interactions for in vitro transcription of promoter-reporter constructs. Results of these studies are expected to provide new knowledge concerning the molecular mechanism of age-dependent changes in AR gene expression. Furthermore, receptor dysregulation is one of the major causes of the age-associated loss of systemic coordination. These studies will therefore, make an important contribution toward an overall understanding of the molecular basis of aging.
在老鼠的一生中,雄性和雌性的肝脏

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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ARUN K. ROY其他文献

Protection of spermatogenesis by α2u globulin in rats treated with oestrogen
雌激素处理大鼠中α2u 球蛋白对精子发生的保护作用
  • DOI:
    10.1038/260719a0
  • 发表时间:
    1976-04-22
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    ARUN K. ROY;JENNIE G. BYRD;NAREN M. BISWAS;AJIT K. CHOWDHURY
  • 通讯作者:
    AJIT K. CHOWDHURY

ARUN K. ROY的其他文献

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{{ truncateString('ARUN K. ROY', 18)}}的其他基金

Aging and Prostatic Hyperplasia in Transgenic Mice
转基因小鼠的衰老和前列腺增生
  • 批准号:
    6471945
  • 财政年份:
    2002
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    6335326
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
Aging and Androgen Gene Regulation
衰老与雄激素基因调控
  • 批准号:
    6547251
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    6137038
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    2001419
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    2051722
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    2692842
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    2855821
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    6590904
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:
AGING AND ANDROGEN RECEPTOR GENE REGULATION
衰老与雄激素受体基因调控
  • 批准号:
    2051725
  • 财政年份:
    1993
  • 资助金额:
    $ 16.1万
  • 项目类别:

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DNA footprinting of a plant defense gene family; to support visit by A.M. Yorkin, Department of Genetics, St. Petersburg State University, St. Petersburg, Russia
植物防御基因家族的 DNA 足迹;
  • 批准号:
    147394-1992
  • 财政年份:
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  • 资助金额:
    $ 16.1万
  • 项目类别:
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