STUDY OF MICE IN WHICH THE TGF BETA 1 GENE HAS BEEN DISRUPTED
STUDY OF MICE IN WHICH THE TGF BETA 1 GENE HAS BEEN DISRUPTED
批准号:
3752781
负责人:
A B ROBERTS
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
转化生长因子-β(转化生长因子-β)此前曾被认为与
在胚胎发育和调节细胞增殖和
目的基因的表达。在三种转化生长因子-β亚型中,1型转化生长因子-β
贝塔既是大多数组织中含量最丰富的,也是最尖锐的
在损伤和修复以及各种疾病的发病机制中都有调节-
艾斯。尽管它们没有任何明显的发育缺陷,但在这些老鼠中
转化生长因子-β1基因已被靶向干扰敲除
约3周龄的多灶性炎症性疾病。我们有
调查了这一炎症综合征中可能的启动事件
并发现,在检测到任何组织渗透之前,表达
I类和II类主要组织相容性抗原在这些细胞中都很高
小鼠,而在正常的可比组织中通常检测不到
提示转化生长因子-β可能是MHC的天然抑制因子
抗原表达。此外,我们发现令人惊讶的正常情况
这些小鼠的发育是通过将转化生长因子-β1蛋白从
杂合子母亲,包括胎盘和乳汁中。通过
服用免疫抑制剂地塞米松,以延长
一个突变等位基因的纯合子女性,我们已经实现了一个术语
分娩并能够证明转化生长因子-β1(-/-)幼崽出生于
转化生长因子-β1(-/-)母亲有严重的发育缺陷,尤其是
在心脏生成方面。正常的心脏生成是由母体支持的
转化生长因子-β1从杂合子母亲转移到转化生长因子-β1(-/-)仔鼠的研究
或通过内源性合成转化生长因子-β1在出生为空的杂合子幼鼠
母亲们。这证明了转化生长因子-β1在
心脏发生;母体转移转化生长因子-β1在正常人中的作用
生理学目前尚不清楚。
英文摘要
Transforming growth factor-beta (TGF-beta) has previously been implicated
in embryonic development and in regulating both cell proliferation and
expression of target genes. Of the three TGF-beta isoforms, type 1 TGF-
beta is both the most abundant in most tissues and the most acutely
regulated in injury and repair and in the pathogenesis of various diseas-
es. Although they lack any obvious developmental defects, mice in which
the TGF-beta1 gene has been knocked out by targeted disruption die at
about 3 weeks of age of multifocal inflammatory disease. We have
investigated the possible initiating event in this inflammatory syndrome
and found that, prior to detection of any tissue infiltrates, expression
of both class I and II major histocompatibility antigens is high in these
mice, while generally undetectable in comparable tissues in normal
littermates, suggesting that TGF-beta may be a natural repressor of MHC
antigen expression. Moreover, we have found that the surprisingly normal
development of these mice results from transfer of TGF-beta1 protein from
the heterozygous mothers, both transplacentally and in the milk. By
dosing with an immunosuppressant, dexamethasone, to extend the life of
a female homozygous for the mutant allele, we have achieved a term
delivery and been able to demonstrate that TGF-beta1 (-/-) pups born to
a TGF-beta1 (-/-) mother have severe developmental defects, especially
in cardiogenesis. Normal cardiogenesis is supported either by maternal
transfer of TGF-beta1 from heterozygous mothers to TGF-beta1 (-/-) pups
or by endogenous synthesis of TGF-beta1 in heterozygous pups born to null
mothers. This demonstrates a critical role of TGF-beta1 in
cardiogenesis; the role of maternal transfer of TGF-beta1 in normal
physiology is not known at present.
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STUDY OF MICE IN WHICH THE TGF BETA GENE HAS BEEN DISRUPTED
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批准号:2463689
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND RECEPTOR SIGNALLING OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:5201457
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:3853409
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
MECHANISM OF ACTION OF TYPE BETA TRANSFORMING GROWTH FACTOR
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批准号:4692310
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
NOVEL CHEMOPREVENTIVE AGENTS IN EXPERIMENTAL MAMMARY CARCINOGENESIS
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批准号:6100875
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:3916749
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:3838326
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
STRUCTURE/FUNCTION AND SIGNAL TRANSDUCTION PATHWAYS OF TGF BETA
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批准号:6160869
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
NOVEL CHEMOPREVENTIVE AGENTS IN EXPERIMENTAL MAMMARY CARCINOGENESIS
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批准号:6160975
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:3752614
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:3774777
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
NOVEL CHEMOPREVENTIVE AGENTS IN EXPERIMENTAL MAMMARY CARCINOGENESIS
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批准号:2463698
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
STUDY OF MICE IN WHICH THE TGF BETA 1 GENE HAS BEEN DISRUPTED
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批准号:5201576
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND RECEPTOR SIGNALLING OF TRANSFORMING GROWTH FACTOR BETA
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批准号:2463600
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA
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批准号:3874617
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA ON CARDIAC CELLS
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批准号:3838479
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
STUDY OF MICE IN WHICH THE TGF BETA GENE HAS BEEN DISRUPTED
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批准号:6160969
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:A B ROBERTS
-
依托单位:
STUDY OF MICE IN WHICH THE TGF BETA GENE HAS BEEN DISRUPTED
-
批准号:6100869
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:A B ROBERTS
-
依托单位:
STRUCTURE/FUNCTION AND SIGNAL TRANSDUCTION PATHWAYS OF TGF BETA
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批准号:6100769
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:A B ROBERTS
-
依托单位:
MECHANISM OF ACTION OF TYPE BETA TRANSFORMING GROWTH FACTOR
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批准号:3963417
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:A B ROBERTS
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依托单位:
海外基金