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
- 来源:
- 关键词:DNA binding protein DNA footprinting aging androgen receptor animal old age computer assisted sequence analysis developmental genetics gel mobility shift assay genetic promoter element genetic regulation genetic regulatory element genetic transcription juvenile animal laboratory rat liver cells mature animal molecular cloning mutant nucleic acid sequence polymerase chain reaction receptor expression reporter genes restriction mapping site directed mutagenesis southern blotting tissue /cell culture transcription factor transfection
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)
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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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:
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