COCAINE REGULATION OF FOSB SPLICING
COCAINE REGULATION OF FOSB SPLICING
批准号:
6260335
负责人:
Judith Ann Potashkin
金额:
$7.8万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-09-30 至 2002-08-31
中文摘要
描述(改编自申请人的摘要):
尽管最近的研究揭示了许多关于人类免疫缺陷的分子基础
在吸毒成瘾方面,我们对变化的认识仍然存在许多差距
与慢性药物摄入相关的基因表达。一个突出的问题
在慢性可卡因暴露时发生的改变是在
转录因子DeltaFosB的非常稳定的亚型纹状体,即
通过FosB转录本的选择性剪接产生。DeltaFosB亚型
可能会调节某些神经和行为的改变
吸毒成瘾。在选择性剪接中起作用的因素
尚未鉴定出deltaFasB。要开始理解
导致稳定的DeltaFosB产生的转录后事件,我们
将检验顺式和反式作用因子都很重要的假设
在这项规定中。为了验证这一假设,FosB的突变分析将是
用于鉴定前信使核糖核酸剪接所必需的序列。交联剂
将进行RNA结合研究,以确定哪些反式作用
在从大脑中制备的剪接提取物中,因子与RNA结合。因素
这些研究中确定的基因将在剪接分析中进行测试,以确定
他们对体外拼接进行了监管。这些研究将确定这些因素
在长期使用可卡因的过程中调节剪接所需的,并导致
对所涉及的机制的理解。因为DeltaFosB也被诱导
通过长期服用安非他明等其他滥用药物,
尼古丁和阿片类药物,这项研究的结果也可能导致
更好地理解吸毒成瘾。
英文摘要
DESCRIPTION(Adapted from applicant's abstract):
Although recent studies have revealed a great deal about the molecular basis of
drug addiction, numerous gaps remain in our understanding of the changes in
gene expression that are associated with chronic drug intake. One prominent
alteration that occurs upon chronic cocaine exposure is accumulation in the
striatum of very stable isoforms of the transcription factor deltaFosB that is
produced by alternative splicing of the fosB transcript. The deltaFosB isoforms
may mediate some of the neural and behavioral modivications that occur with
drug addiction. The factors that play a role in the alternative splicing of
deltaFasB have not yet been identified. To begin to understand the
posttranscriptional events that lead to the production of stable deltaFosB, we
will test the hypothesis that both cis- and trans-acting factors are important
in this regulation. To test this hypothesis, mutation analysis of fosB will be
used to identify the sequences essential for pre-mRNA splicing. Cross linking
and RNA binding studies will be undertaken to determine which trans acting
factors bind to the RNA in splicing extracts prepared from brains. Factors
identified in these studies will be tested in splicing assays to determine if
they regulate splicing invitro. These studies will identify the factors
required for the regulation of splicing during chronic- cocaine use and lead to
an understanding of the mechanisms involved. Because deltaFosB is also induced
by chronic administration of other drugs of abuse, such as amphetamine,
nicotine and opiates, the results obtained in this study may also lead to a
better understanding of drug addiction.
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会议论文
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依托单位:
Cocaine Regulation of FosB Splicing
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批准号:6612675
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项目类别:
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资助金额:$23.4万
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财政年份:2002
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依托单位:
Cocaine Regulation of FosB Splicing
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批准号:6506030
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项目类别:
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资助金额:$23.4万
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财政年份:2002
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负责人:Judith Ann Potashkin
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依托单位:
Cocaine Regulation of FosB Splicing
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批准号:6768745
-
项目类别:
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资助金额:$23.4万
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财政年份:2002
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负责人:Judith Ann Potashkin
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依托单位:
COCAINE REGULATION OF FOSB SPLICING
-
批准号:6379099
-
项目类别:
-
资助金额:$7.8万
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财政年份:2000
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负责人:Judith Ann Potashkin
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依托单位:
FISSION YEAST PREMRNA SPLICING FACTORS
-
批准号:2184948
-
项目类别:
-
资助金额:$14.76万
-
财政年份:1992
-
负责人:Judith Ann Potashkin
-
依托单位:
FISSION YEAST PRE-MRNA SPLICING FACTORS
-
批准号:3306992
-
项目类别:
-
资助金额:$12.97万
-
财政年份:1992
-
负责人:Judith Ann Potashkin
-
依托单位:
FISSION YEAST PRE-MRNA SPLICING FACTORS
-
批准号:3306993
-
项目类别:
-
资助金额:$12.36万
-
财政年份:1992
-
负责人:Judith Ann Potashkin
-
依托单位:
FISSION YEAST PREMRNA SPLICING FACTORS
-
批准号:2184950
-
项目类别:
-
资助金额:$14.07万
-
财政年份:1992
-
负责人:Judith Ann Potashkin
-
依托单位:
FISSION YEAST PREMRNA SPLICING FACTORS
-
批准号:2184949
-
项目类别:
-
资助金额:$13.75万
-
财政年份:1992
-
负责人:Judith Ann Potashkin
-
依托单位:
CHARACTERIZATION OF CDC 2 GENE PRODUCT OF FISSION YEAST
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批准号:3040989
-
项目类别:
-
资助金额:$2.5万
-
财政年份:1987
-
负责人:Judith Ann Potashkin
-
依托单位:
CHARACTERIZATION OF CDC 2 GENE PRODUCT OF FISSION YEAST
-
批准号:3040988
-
项目类别:
-
资助金额:$2.0万
-
财政年份:1986
-
负责人:Judith Ann Potashkin
-
依托单位:
CHARACTERIZATION OF CDC 2 GENE PRODUCT OF FISSION YEAST
-
批准号:3040987
-
项目类别:
-
资助金额:$1.9万
-
财政年份:1986
-
负责人:Judith Ann Potashkin
-
依托单位:
海外基金