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    Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease
    106.
    发明授权
    Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease 失效
    表达APP-Swedish突变的转基因小鼠发展成进行性神经系统疾病

    公开(公告)号：US5877399A

    公开(公告)日：1999-03-02

    申请号：US664872

    申请日：1996-06-17

    申请人： Karen Hsiao ,  David R. Borchelt ,  Sangram S. Sisodia

    发明人： Karen Hsiao ,  David R. Borchelt ,  Sangram S. Sisodia

    IPC分类号： A01K67/027 ,  A61K38/00 ,  A61K45/00 ,  A61K49/00 ,  A61P25/28 ,  C07K14/47 ,  C12N15/09 ,  C12N15/85 ,  C12N5/00 ,  C12N15/00

    CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  A61K49/0008 ,  C07K14/4711 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0312 ,  A01K2267/0318 ,  A01K2267/0343 ,  A01K2267/0356 ,  A61K38/00 ,  C12N2830/008

    摘要： Provided is a transgenic non-human eukaryotic animal whose germ cells and somatic cells contain the amyloid precursor protein sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage. In mice, an age-related CNS disorder characterized by agitation, neophobia, seizures, inactivity, diminished cerebral glucose utilization, cortico-limbic gliosis, and death, develops. An acceleration of this disorder occurs in transgenic mice expressing human and mouse Alzheimer amyloid precursor proteins (APP) produced using a hamster prion protein gene-derived cosmid vector that confers position-independent, copy number-dependent expression. In transgenic mice the disorder develops in direct relationship to brain levels of transgenic APP, but mutant APP confers the phenotype at lower levels of expression than wild-type APP. The disorder occurs in the absence of extracellular amyloid deposition, indicating that some pathogenic activities of APP are dissociated from amyloid formation.

    摘要翻译： 提供了一种转基因非人类真核动物，其生殖细胞和体细胞在胚胎期含有引入动物或动物祖先的淀粉样蛋白前体蛋白质序列。 在小鼠中，发展为以激动，恐惧症，癫痫发作，不活动，脑葡萄糖利用减少，皮层边缘胶质增生和死亡为特征的年龄相关的中枢神经系统疾病。 这种疾病的加速发生在使用赋予与位置无关的拷贝数依赖性表达的仓鼠朊蛋白基因衍生的粘粒载体产生的表达人和小鼠阿尔茨海默氏淀粉样蛋白前体蛋白（APP）的转基因小鼠中。 在转基因小鼠中，病症与转基因APP的脑水平直接相关，但是突变体APP赋予表型低于野生型APP的表型。 该疾病发生在没有细胞外淀粉样蛋白沉积的情况下，表明APP的一些致病活性与淀粉样蛋白形成分离。

    Transgenic mouse as model for diseases involving dopaminergic dysfunction
    109.
    发明授权
    Transgenic mouse as model for diseases involving dopaminergic dysfunction 失效
    转基因小鼠作为涉及多巴胺能障碍的疾病的模型

    公开(公告)号：US5723719A

    公开(公告)日：1998-03-03

    申请号：US389191

    申请日：1995-02-15

    申请人： Anil K. Ratty ,  Stanley D. Glick ,  John J. Mullins ,  Lawrence W. Fitzgerald ,  Kenneth W. Gross

    发明人： Anil K. Ratty ,  Stanley D. Glick ,  John J. Mullins ,  Lawrence W. Fitzgerald ,  Kenneth W. Gross

    IPC分类号： A61K49/00 ,  C12N9/64 ,  C12N15/85 ,  C12N5/00 ,  C12N15/00

    CPC分类号： A01K67/0276 ,  A61K49/0008 ,  C12N15/8509 ,  C12N9/6486 ,  C12Y304/23015 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356

    摘要： The present invention provides a transgenic mouse which exhibits a circling phenotype as a result of insertional mutagenesis. The insertional mutant was caused by introducing genetic material into the genome of the mouse, or an ancestor thereof, at an embryonic stage. The genetic material appears to alter or disrupt an endogenous genetic locus affecting motor function, resulting in the mutation. More particularly, transgenic mouse lines were made by microinjection of about 24 kb XhoI genomic DNA fragment containing the mouse Ren-2.sup.d renin gene into BCF.sub.1, fertilized eggs. One transgenic mouse line, designated TgX15 (also known as chakragati mice), bred to homozygosity was found to exhibit a circling phenotype. The transgenic mouse line TgX15 may be an important resource for investigating the molecular genetic mechanisms that determine specific aspects of brain function and behavior. Also, these mice may be useful to evaluate new and potentially more effective agents for the therapeutic treatment of disorders involving dopaminergic dysfunction such as Parkinsonism and schizophrenia.

    摘要翻译： 本发明提供了作为插入诱变的结果显示盘旋表型的转基因小鼠。 插入突变体是通过在胚胎阶段将遗传物质引入小鼠或其祖先的基因组中引起的。 遗传物质似乎改变或破坏影响运动功能的内源遗传基因，导致突变。 更具体地，通过将​​含有小鼠Ren-2d肾素基因的约24kb XhoI基因组DNA片段显微注射到BCF1受精卵中制备转基因小鼠品系。 发现称为TgX15（也称为chakragati小鼠）的一种转基因小鼠品系，其育种为纯合子，表现出循环表型。 转基因小鼠品系TgX15可能是调查确定脑功能和行为特定方面的分子遗传机制的重要资源。 此外，这些小鼠可用于评估新的和潜在的更有效的药物治疗涉及多巴胺能功能障碍的疾病如帕金森综合征和精神分裂症。