公开(公告)号：US06815575B1

公开(公告)日：2004-11-09

申请号：US09639207

申请日：2000-08-14

申请人： Parsa Kazemi-Esfarjani ,  Seymour Benzer

发明人： Parsa Kazemi-Esfarjani ,  Seymour Benzer

IPC分类号： A01K67033

CPC分类号： A01K67/0333 ,  A01K67/0339 ,  A01K2217/05 ,  A01K2267/03 ,  A61K49/0008 ,  C07K14/43581

摘要： The present invention is based on an in vivo animal model that mimics human cellular and tissue degenerative disorders. The animal model exhibits cellular toxicity in response to expanded polyglutamine repeat sequences. The animal model is therefore useful for identifying genes or other compounds that modulate cellular and tissue degeneration and cell survival, for example, in neural, muscle, mesoderm, kidney and other tissues associated with frontotemporal dementia, prion diseases, polyglutamine disorders and protein aggregation disorders, Genes that suppress degeneration identified using the animal model include HDJ1, TPR2 and MLF. These genes, and their human homologues, functional fragments and probes are therefore useful in treating such disorders and for diagnostic purposes. Accordingly, methods for identifying nucleic acids and other compounds that modulate frontotemporal dementia, prion diseases, polyglutamine disorders and protein aggregation disorders is therefore provided. Pharmaceutical compositions comprising HDJ1, TPR2 and, MLF genes, and subsequences encoding functional polypeptides are also provided, as they are useful in treating such degenerative disorders.

摘要翻译： 本发明基于模拟人细胞和组织退行性疾病的体内动物模型。 动物模型响应扩展的多聚谷氨酰胺重复序列显示细胞毒性。 因此，动物模型可用于识别调节细胞和组织变性和细胞存活的基因或其他化合物，例如在神经，肌肉，中胚层，肾和与额颞叶痴呆相关的其它组织，朊病毒疾病，聚谷氨酰胺病症和蛋白质聚集障碍 使用动物模型鉴定的抑制变性的基因包括HDJ1，TPR2和MLF。 因此，这些基因及其人类同源物，功能片段和探针可用于治疗这些疾病和用于诊断目的。 因此，提供了用于鉴定调节额颞叶痴呆，朊病毒病，聚谷氨酰胺病症和蛋白质聚集障碍的核酸和其它化合物的方法。 还提供包含HDJ1，TPR2和MLF基因以及编码功能性多肽的亚序列的药物组合物，因为它们可用于治疗这种退行性疾病。