TRANSGENIC MODEL FOR DELAY-TYPE HYPERSENSITIVITY (DTH) AND USE THEREOF
    1.
    发明申请
    TRANSGENIC MODEL FOR DELAY-TYPE HYPERSENSITIVITY (DTH) AND USE THEREOF 有权
    用于延迟型超高频(DTH)的转换模型及其用途

    公开(公告)号:US20160037757A1

    公开(公告)日:2016-02-11

    申请号:US14620141

    申请日:2015-02-11

    Abstract: The present invention provides an in vivo platform for identifying and determining therapeutic or prophylactic activity of test compounds in delay-type hypersensitivity (DTH) and other inflammatory or cancerous diseases mediated by activation of IKK-βC46A mutants. The in vivo platform of the present invention is a non-human transgenic mammal, e.g., a mouse model, with a site directed mutagenesis at a cysteine residue replaced by alanine in IKK-β protein kinase. The site directed mutagenesis is introduced by a specially designed targeting vector containing a transversion in exon 3 of the Ikbkb genes encoding the IKK-β. The present invention also provides methods for generating the transgenic mammal and for determining and identifying compounds that can inhibit activation of IKK-βC46A mutants.

    Abstract translation: 本发明提供了一种用于鉴定和确定延迟型超敏反应(DTH)和通过IKK-和bgr C46A突变体的活化介导的其它炎性或癌性疾病的测试化合物的治疗或预防活性的体内平台。 本发明的体内平台是非人转基因哺乳动物,例如小鼠模型,在IKK-和bgr中被半胱氨酸残基替换为丙氨酸的位点定向诱变; 蛋白激酶。 通过特异设计的靶向载体引入定点诱变,所述靶向载体在编码IKK-&bgr的Ikbkb基因的外显子3中含有颠换。 本发明还提供了产生转基因哺乳动物以及用于测定和鉴定可以抑制IKK-Bgr C46A突变体活化的化合物的方法。

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