MAPPING SUSCEPTIBILITY GENES IN MURINE COLITIS

绘制小鼠结肠炎的易感基因图谱

基本信息

  • 批准号:
    6648572
  • 负责人:
  • 金额:
    $ 25.04万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-09-01 至 2003-08-31
  • 项目状态:
    已结题

项目摘要

Pathogenesis if inflammatory bowel disease (IBD) in humans is multi- factorial, involving complex interactions among genetic, environmental, and immunological factors. Genetic disruption of the Interleukin-10 ((Il10) gene in mice predisposes to spontaneous development of IBD. However, the severity and extent of the IBD syndrome is controlled by as yet unidentified genetic background modifiers. A severe juvenile-onset colitis in cecum, proximal, middle, and distal colon is elicited by IL-10 deficiency in C3H mice by 4 weeks of age, whereas the B6-IL10-/- have developed little or no lesions by 12 weeks of age. Project 4 of this Program Project grant proposes to use quantitative trait locus (QTL) mapping techniques to identify the genetic basis for these differential strain susceptibilities, and to use this information to indicate relevant phenotypes and thus, candidate genes, for testing in IBD-susceptible humans. The validity of this approach was demonstrated during the previous support in which 6 chromosomal regions were identified that contained genes controlling differential strain susceptibility to experimental colitis induced by dextran sulfate sodium. The specific aims of the project are (1) to use genetic segregation analyses to establish the chromosomal locations of colitis susceptibility loci that confer significantly more severe colitis in C3H/HeJBir.IL10-/- mice and (2) to validate phenotypic effects of colitis loci by producing interval-specific congenic stocks of C3H mice carrying putative resistance alleles from B6, and reciprocally, B6 stocks carrying putative susceptibility alleles from C3H. This approaches should allow fine mapping and candidate gene testing for IBD-predisposing background genes required to interact deleteriously with an inadequately suppressed effector population. Delineation of the genetic mechanisms predisposing to IBD in these mouse models will suggest likely pathways for therapeutic intervention in humans and possibly even allow identification of homologous human genes.
人类炎症性肠病(IBD)的发病机制是多因素的,涉及遗传、环境和免疫因素之间的复杂相互作用。小鼠白细胞介素10(IL 10)基因的遗传破坏易诱发IBD的自发发展。然而,IBD综合征的严重程度和范围是由尚未鉴定的遗传背景修饰剂控制的。在盲肠、近端、中间和远端结肠中的严重的青少年发作的结肠炎由C3 H小鼠中4周龄时的IL-10缺乏引起,而B6-IL 10-/-小鼠在12周龄时几乎没有或没有发生病变。该计划项目资助的项目4建议使用数量性状基因座(QTL)作图技术来确定这些差异菌株亲和性的遗传基础,并使用这些信息来指示相关表型,从而指示候选基因,用于IBD易感人群的测试。这种方法的有效性在之前的支持中得到了证明,其中鉴定了6个染色体区域,这些区域含有控制对葡聚糖硫酸钠诱导的实验性结肠炎的差异菌株易感性的基因。该项目的具体目的是(1)使用遗传分离分析来确定结肠炎易感基因座的染色体位置,这些基因座在C3 H/HeJBir.IL10-/-小鼠中赋予显著更严重的结肠炎,以及(2)通过产生携带来自B6和B10的推定抗性等位基因的C3 H小鼠的间隔特异性同源原种来验证结肠炎基因座的表型效应。携带来自C3 H的推定易感性等位基因的B6原种。这种方法应该允许精细定位和候选基因检测IBD易感背景基因需要有害地与一个不充分抑制效应人口。在这些小鼠模型中,对IBD易感性遗传机制的描述将为人类的治疗干预提供可能的途径,甚至可能允许鉴定同源的人类基因。

项目成果

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EDWARD H LEITER其他文献

EDWARD H LEITER的其他文献

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{{ truncateString('EDWARD H LEITER', 18)}}的其他基金

New Insights into Animals Models of Diabetes
对糖尿病动物模型的新见解
  • 批准号:
    6672894
  • 财政年份:
    2003
  • 资助金额:
    $ 25.04万
  • 项目类别:
MAPPING SUSCEPTIBILITY GENES IN MURINE COLITIS
绘制小鼠结肠炎的易感基因图谱
  • 批准号:
    6496704
  • 财政年份:
    2001
  • 资助金额:
    $ 25.04万
  • 项目类别:
NEW MOUSE MODELS OF DIABESITY
新的糖尿病小鼠模型
  • 批准号:
    6194024
  • 财政年份:
    2001
  • 资助金额:
    $ 25.04万
  • 项目类别:
NEW MOUSE MODELS OF DIABESITY
新的糖尿病小鼠模型
  • 批准号:
    6517693
  • 财政年份:
    2001
  • 资助金额:
    $ 25.04万
  • 项目类别:
MAPPING SUSCEPTIBILITY GENES IN MURINE COLITIS
绘制小鼠结肠炎的易感基因图谱
  • 批准号:
    6340868
  • 财政年份:
    2000
  • 资助金额:
    $ 25.04万
  • 项目类别:
BECKMAN SYNCHRON CX5 DELTA CHEMISTRY ANALYSIS SYSTEM
Beckman SYNCHRON CX5 Delta 化学分析系统
  • 批准号:
    2766454
  • 财政年份:
    1999
  • 资助金额:
    $ 25.04万
  • 项目类别:
MAPPING SUSCEPTIBILITY GENES IN MURINE COLITIS
绘制小鼠结肠炎的易感基因图谱
  • 批准号:
    6190084
  • 财政年份:
    1999
  • 资助金额:
    $ 25.04万
  • 项目类别:
NEW MODELS FOR IDENTIFYING NIDDM POLYGENES
鉴定 NIDDM 多基因的新模型
  • 批准号:
    6122951
  • 财政年份:
    1998
  • 资助金额:
    $ 25.04万
  • 项目类别:
NEW MODELS FOR IDENTIFYING NIDDM POLYGENES
鉴定 NIDDM 多基因的新模型
  • 批准号:
    6253949
  • 财政年份:
    1997
  • 资助金额:
    $ 25.04万
  • 项目类别:
MOUSE MODELS FOR HUMAN DISEASES
人类疾病小鼠模型
  • 批准号:
    2546597
  • 财政年份:
    1993
  • 资助金额:
    $ 25.04万
  • 项目类别:

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