公开(公告)号：US5917124A

公开(公告)日：1999-06-29

申请号：US927986

申请日：1997-09-12

申请人： Jeffrey I. Gordon ,  Emily M. Garabedian

发明人： Jeffrey I. Gordon ,  Emily M. Garabedian

IPC分类号： A01K67/027 ,  C07K14/82 ,  C12N15/85 ,  A61F2/30

CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  C07K14/82 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0331

摘要： Disclosed are transgenic mice that produces prostate tumors and faithfully recapitulate many of the features of human prostatic carcinoma. It has been discovered that transcriptional regulatory elements active in Paneth cells, granule goblet cells, intermediate cells, or a combination, when used to express Simian Virus 40 large T antigen (TAg) in a transgenic mouse leads to development of prostate tumors in the mouse. The transcriptional regulatory elements are derived from the cryptdin-2 (CR2) gene. The disclosed mice develop prostatic intraepithelial neoplasia (PIN) at an early age. Progression with local invasion, loss of androgen-dependence and eventual metastases are hallmarks of the disclosed transgenic mice. Preferred embodiments of the disclosed transgenic mice have several important characteristics: (1) the disease is fully penetrant--all mice containing the SV40 TAg transgene develop prostatic cancer; (2) the first appearance of SV40 TAg always coincides with the appearance of cellular atypia in prostatic acini; (3) the rate of progression of the neoplasia is rapid; (4) prostatic adenocarcinomas in the transgenic mice exhibit foci of neuroendocrine differentiation; (5) metastatic lesions are common in the lymph nodes, liver, lung, and bone of the disclosed transgenic mice and are evident early in life; and (6) the lifespan of the disclosed transgenic animals is not shortened by transgene-related pathology in other organs--female transgenic mice develop normally and have a normal lifespan.

摘要翻译： 公开了产生前列腺肿瘤并忠实地重现人类前列腺癌的许多特征的转基因小鼠。 已经发现，当用于在转基因小鼠中表达猿猴病毒40大T抗原（TAg）时，在Paneth细胞，颗粒状杯状细胞，中间细胞或组合中活跃的转录调节元件导致小鼠中前列腺肿瘤的发展 。 转录调节元件衍生自cryptdin-2（CR2）基因。 所公开的小鼠在早期发展为前列腺上皮内瘤变（PIN）。 本地入侵，丧失雄激素依赖性和最终转移的进展是所公开的转基因小鼠的标志。 所公开的转基因小鼠的优选实施方案具有几个重要特征：（1）该疾病是完全渗透的，所有含有SV40TT转基因的小鼠均发展为前列腺癌; （2）SV40的首次出现TAg始终与前列腺炎的细胞异型现象相吻合; （3）瘤形成进展迅速; （4）前列腺腺癌转基因小鼠表现出神经内分泌分化的病灶; （5）转移性病变在所公开的转基因小鼠的淋巴结，肝，肺和骨中是常见的，并且在生命早期是明显的; 和（6）所公开的转基因动物的寿命不会因其他器官中的转基因相关病理学而缩短 - 雌性转基因小鼠正常发育并具有正常的寿命。