Gene Targeted Mice With A Simplified Immune System

具有简化免疫系统的基因靶向小鼠

基本信息

项目摘要

DESCRIPTION (provided by applicant): Gene-targeted mice with a simplified immune system clonal selection demands that individual B cells be monospecific. Allelic and isotypic exclusion ensure that there is but one functional heavy (H) chain and one functional light (L) chain gene. While there is general agreement that allelic and isotypic exclusion of L chain is accomplished by turning off the enzymes that assemble the genes from gene segments, various competing theories have been proposed to explain allelic exclusion at the H-chain locus. The goal of this proposal is to assess the contributions of the stochastic, genetic regulation, and cellular regulation models to the understanding of allelic exclusion at the immunoglobulin H-chain locus. Because we have obtained some indication that the pre-B-cell population contains cells with two productively rearranged H alleles, we propose to determine the frequency of the double H producers in mice with germ line H and L loci, and in the presence of preformed H and L genes. Because the products of the mu and delta alleles can be easily distinguished by immunofluorescence, we will use mice in which one C-mu allele is knocked out. Furthermore, we will test the various hypotheses in the monoclonal B-cell mouse generated by nuclear transfer from a B lymphocyte. In the proposed experiments, the H and L alleles from the original B lymphocyte will be shuffled and combined with germ line or nonfunctional alleles. The aim is to create mice that represent various pre-B- and B-cell genotypes, and to investigate the effect of the various preformed alleles on the germ line or rearranged allele(s) and on B-cell development as it relates to allelic exclusion.
描述(由申请人提供):具有简化免疫系统克隆选择的基因靶向小鼠要求单个B细胞是单特异性的。等位基因和同种型排除确保只有一个功能性重(H)链和一个功能性轻(L)链基因。虽然人们普遍认为L链的等位基因和同型排斥是通过关闭从基因片段组装基因的酶来完成的,但已经提出了各种竞争理论来解释H链位点的等位基因排斥。该建议的目的是评估随机,遗传调控和细胞调控模型的贡献,以了解等位基因排斥在免疫球蛋白H链基因座。 因为我们已经获得了一些迹象表明,前B细胞群体包含两个生产重排H等位基因的细胞,我们建议确定的频率双H生产商在生殖系H和L基因座的小鼠,并在预先形成的H和L基因的存在。因为mu和delta等位基因的产物可以通过免疫荧光容易地区分,所以我们将使用其中一个C-mu等位基因被敲除的小鼠。此外,我们将在通过B淋巴细胞核转移产生的单克隆B细胞小鼠中测试各种假设。在所提出的实验中,来自原始B淋巴细胞的H和L等位基因将被改组并与生殖系或非功能性等位基因组合。目的是创建代表各种前B细胞和B细胞基因型的小鼠,并研究各种预先形成的等位基因对生殖系或重排等位基因以及与等位基因排斥相关的B细胞发育的影响。

项目成果

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MATTHIAS R WABL其他文献

MATTHIAS R WABL的其他文献

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{{ truncateString('MATTHIAS R WABL', 18)}}的其他基金

Peptides presented by DNA-specific B lymphocytes in lupus
狼疮中 DNA 特异性 B 淋巴细胞呈递的肽
  • 批准号:
    8930442
  • 财政年份:
    2014
  • 资助金额:
    $ 31.71万
  • 项目类别:
Gene Targeted Mice with a Simplified Immune System
具有简化免疫系统的基因靶向小鼠
  • 批准号:
    8088482
  • 财政年份:
    2010
  • 资助金额:
    $ 31.71万
  • 项目类别:
Tumor Suppressors in Lymphocytes
淋巴细胞中的肿瘤抑制因子
  • 批准号:
    7027215
  • 财政年份:
    2006
  • 资助金额:
    $ 31.71万
  • 项目类别:
Tumor Suppressors in Lymphocytes
淋巴细胞中的肿瘤抑制因子
  • 批准号:
    7325816
  • 财政年份:
    2006
  • 资助金额:
    $ 31.71万
  • 项目类别:
Tumor Suppressors in Lymphocytes
淋巴细胞中的肿瘤抑制因子
  • 批准号:
    7231727
  • 财政年份:
    2006
  • 资助金额:
    $ 31.71万
  • 项目类别:
GENE TARGETED MICE WITH A SIMPLIFIED IMMUNE SYSTEM
具有简化免疫系统的基因靶向小鼠
  • 批准号:
    6373658
  • 财政年份:
    1998
  • 资助金额:
    $ 31.71万
  • 项目类别:
Gene Targeted Mice with a Simplified Immune System
具有简化免疫系统的基因靶向小鼠
  • 批准号:
    8465786
  • 财政年份:
    1998
  • 资助金额:
    $ 31.71万
  • 项目类别:
Gene Targeted Mice with a Simplified Immune System
具有简化免疫系统的基因靶向小鼠
  • 批准号:
    8278599
  • 财政年份:
    1998
  • 资助金额:
    $ 31.71万
  • 项目类别:
Gene Targeted Mice with a Simplified Immune System
具有简化免疫系统的基因靶向小鼠
  • 批准号:
    8663161
  • 财政年份:
    1998
  • 资助金额:
    $ 31.71万
  • 项目类别:
Gene Targeted Mice with a Simplified Immune System
具有简化免疫系统的基因靶向小鼠
  • 批准号:
    8077966
  • 财政年份:
    1998
  • 资助金额:
    $ 31.71万
  • 项目类别:

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