MURINE MODELS OF THE WISKOTT ALDRICH SYNDROME
MURINE MODELS OF THE WISKOTT ALDRICH SYNDROME
批准号:
6346233
负责人:
FRED S. ROSEN
金额:
$42.66万
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:
2000-09-01 至 2001-08-31
中文摘要
Wiskott-Aldrich综合征(WAS)是一种血液系统疾病,
其特征在于T细胞和B细胞免疫缺陷、湿疹,
血小板减少症 有缺陷的蛋白质(WASP)被认为是发挥作用,
在造血细胞的复杂信号通路中起关键作用,
涉及细胞表面信号和细胞骨架的协调
结构变化。 最近,我们已经破坏了小鼠中的WAS基因,
胚胎干(ES)细胞,并使用RAG 2缺陷胚泡
互补系统,以显示WASP缺陷型小鼠淋巴细胞具有
与WAS患者中的缺陷非常相似的增殖缺陷。
此外,我们还鉴定了几种细胞信号分子,
包括Cdc 42,它们与WASP相互作用。 最后,我们确定了
第二个WASP家族成员(N-WASP.这
该项目旨在建立这些研究,以建立一个小鼠模型,
的WAS,并进一步阐明WASP和WASP相关的功能,
proteins. 我们的第一个目标是描述功能的缺陷,
WASP和WASP相关蛋白。 我们的首要目标是描述缺陷的特征
WASP缺陷小鼠的免疫系统。 我们的第二个目标是
通过基因靶向突变和遗传学评估N-WASP功能
比较接近。 第三个目标是雇佣人类WASP-
血小板缺陷和WASP缺陷小鼠研究WASP在
血小板的产生和功能。 我们的最终目标是阐明
WASP和N-WASP的功能结构域通过遗传互补
接近。 这些研究应该提供进一步的洞察力,
与WAS相关的发病机制,同时提供更一般的见解
WASP家族蛋白在细胞内信号通路中的作用
控制着细胞骨架重组
英文摘要
The Wiskott-Aldrich syndrome (WAS) is a hematological disorder
characterized by a T-and B-cell immunodeficiency, eczema, and
thrombocytopenia. The defective protein (WASP) is thought to play a
critical role in a complex signaling pathway in hematopoietic cells that
involves the coordination of cell surface signals and cytoskeletal
structural changes. Recently, we have disrupted the WAS gene in murine
embryonic stem (ES) cells and used the RAG2-deficient blastocyst
complementation system to show that WASP-deficient murine lymphocytes have
proliferation defects that closely resemble the defects in WAS patients.
In addition, we have identified several cellular signaling molecules,
including Cdc42, that interact with WASP. Finally, we have identified th
human and murine homologues of the second WASP-family member (N-WASP. This
project seeks to build on these studies to establish a murine model for
the WAS and to further elucidate the function of WASP and WASP-related
proteins. Our first aim is to characterize defects of the function of
WASP and WASP-related proteins. Our first aim is to characterize defects
of the immune system in WASP-deficient mice. Our second goal is to
evaluate N-WASP function by gene targeted mutational and genetic
comlementation approaches. The third goal is to employ human WASP-
deficient platelets and WASP-deficient mice to study the role of WASP in
platelet production and function. Our final goal is to elucidate
functional domains of WASP and N-WASP by genetic complementation
approaches. These studies should provide further insight into the
pathogenesis associated with WAS while providing more general insights
into the role of WASP-family proteins in intracellular signaling pathways
that control cytoskeletal reorganization.
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会议论文
Analysis of Rho family GTPases and WASp's in blood cells
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批准号:6702498
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项目类别:
-
资助金额:$41.11万
-
财政年份:2002
-
负责人:FRED S. ROSEN
-
依托单位:
MURINE MODELS OF THE WISKOTT ALDRICH SYNDROME
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批准号:6496052
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项目类别:
-
资助金额:$22.05万
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财政年份:2001
-
负责人:FRED S. ROSEN
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依托单位:
EPICS XL-MCL FLOW CYTOMETRY SYSTEM
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批准号:6052297
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项目类别:
-
资助金额:$11.1万
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财政年份:2000
-
负责人:FRED S. ROSEN
-
依托单位:
CHROMOSOME 6P AND DEVELOPMENTAL DEFECTS
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批准号:6637927
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项目类别:
-
资助金额:$29.48万
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财政年份:1999
-
负责人:FRED S. ROSEN
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依托单位:
CHROMOSOME 6P AND DEVELOPMENTAL DEFECTS
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批准号:6182387
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项目类别:
-
资助金额:$27.12万
-
财政年份:1999
-
负责人:FRED S. ROSEN
-
依托单位:
CHROMOSOME 6P AND DEVELOPMENTAL DEFECTS
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批准号:6387704
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项目类别:
-
资助金额:$27.93万
-
财政年份:1999
-
负责人:FRED S. ROSEN
-
依托单位:
CHROMOSOME 6P AND DEVELOPMENTAL DEFECTS
-
批准号:6536108
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项目类别:
-
资助金额:$28.77万
-
财政年份:1999
-
负责人:FRED S. ROSEN
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依托单位:
CLASSICAL COMPLEMENT PATHWAY IN B CELL FUNCTION
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批准号:6085415
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项目类别:
-
资助金额:$26.69万
-
财政年份:1999
-
负责人:FRED S. ROSEN
-
依托单位:
MURINE MODELS OF THE WISKOTT ALDRICH SYNDROME
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批准号:6202580
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项目类别:
-
资助金额:$42.66万
-
财政年份:1999
-
负责人:FRED S. ROSEN
-
依托单位:
MURINE MODELS OF THE WISKOTT ALDRICH SYNDROME
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批准号:6110916
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项目类别:
-
资助金额:$42.66万
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财政年份:1998
-
负责人:FRED S. ROSEN
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依托单位:
STUDY OF RECOVERY AND HALF LIFE OF C1 INHIBITOR VAPOR HEATED IMMUNO II
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批准号:6251936
-
项目类别:
-
资助金额:$1.92万
-
财政年份:1997
-
负责人:FRED S. ROSEN
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依托单位:
SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
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批准号:2771622
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项目类别:
-
资助金额:$213.28万
-
财政年份:1997
-
负责人:FRED S. ROSEN
-
依托单位:
SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
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批准号:6560508
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项目类别:
-
资助金额:$157.69万
-
财政年份:1997
-
负责人:FRED S. ROSEN
-
依托单位:
SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
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批准号:6056471
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项目类别:
-
资助金额:$227.2万
-
财政年份:1997
-
负责人:FRED S. ROSEN
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依托单位:
SAFETY/TOLERANCE OF IMMUNOTHERAPY--AUTOLOGOUS/EX VIVO EXPANDED, HIV SPEC T CELLS
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批准号:6251914
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项目类别:
-
资助金额:$1.92万
-
财政年份:1997
-
负责人:FRED S. ROSEN
-
依托单位:
SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
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批准号:6184076
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项目类别:
-
资助金额:$232.98万
-
财政年份:1997
-
负责人:FRED S. ROSEN
-
依托单位:
SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
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批准号:6697462
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项目类别:
-
资助金额:$160.8万
-
财政年份:1997
-
负责人:FRED S. ROSEN
-
依托单位:
SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
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批准号:6389807
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项目类别:
-
资助金额:$239.18万
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财政年份:1997
-
负责人:FRED S. ROSEN
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依托单位:
HUMAN C1 INHIBITOR IN HEREDITARY AND ACQUIRED ANGIOEDEMA
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批准号:6251880
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项目类别:
-
资助金额:$1.92万
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财政年份:1997
-
负责人:FRED S. ROSEN
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依托单位:
MURINE MODELS OF THE WISKOTT ALDRICH SYNDROME
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批准号:6242871
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项目类别:
-
资助金额:$38.11万
-
财政年份:1997
-
负责人:FRED S. ROSEN
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依托单位:
海外基金