A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animals
A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animals
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DOI：
10.1677/jme.1.01722
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发表时间：
2005-10-01
影响因子：
3.5
通讯作者：
Chung, LWK
中科院分区：
文献类型：
--
作者：
Hsieh, CL;Xie, Z;Chung, LWK
已经开发了许多前列腺癌发生的小鼠模型，但迄今为止还没有可以在活体动物中对前列腺进行成像的模型。在此产生的转基因模型使用萤火虫荧光素酶在小但高活性和特异性的超前列腺特异性抗原（sPSA）启动子的控制下靶向小鼠前列腺。我们使用生物发光成像技术评价了成年转基因小鼠出生后前列腺的发育、退化和雄激素诱导的前列腺生长恢复。研究结果表明：（1）雄性后代的前列腺直到性成熟后才产生显著的生物发光信号。在前列腺和附睾头的腹侧和背外侧叶的腔上皮细胞中检测到荧光素酶，在评价的其他18个器官中几乎没有或没有活性。(ii)虽然在5至35周龄的小鼠前列腺中检测到恒定的高水平生物发光，但在36至54周时检测到生物发光略有下降。(iii)阉割后，荧光素酶活性信号与小鼠前列腺检测的冷却电荷耦合器件相机显着减少。在雄激素给药后，该信号可以迅速恢复到去势前水平。雄激素诱导的荧光素酶活性在最后一次注射后5天下降到接近基础水平。这些数据表明，在（sPSA）启动子的控制下，荧光素酶活性仅限于前列腺的生物发光小鼠模型可以在活体动物中实时使用，以研究前列腺对外源性雄激素的发育和反应性。该模型可以扩展到检测前列腺对治疗的反应性，并用作创始人菌株，以可视化具有不同遗传背景的宿主中的肿瘤。
Numerous mouse models of prostate carcinogenesis have been developed, but hitherto there has been no model in which the prostate gland could be imaged in live animals. The transgenic model generated here targeted mouse prostate gland using a firefly luciferase enzyme under the control of a small but highly active and specific supra prostate-specific antigen (sPSA) promoter. We evaluated postnatal prostate development, involution and androgen-induced restoration of prostate growth in adult transgenic mice using bioluminescence imaging. Results of our study showed that: (i) the prostate gland of male offspring did not yield a significant bioluminescence signal until after sexual maturity. Luciferase was detected in the luminal epithelial cells of the ventral and dorsolateral lobes of the prostate gland and Caput epididymis, with little or no activity in 18 other organs evaluated. (ii) While a constant high level of bioluminescence was detected in the mouse prostate from 5 to 35 weeks of age, a slight drop in bioluminescence was detected at 36 to 54 weeks. (iii) Upon castration, the luciferase activity signal associated with mouse prostate detected by a cooled charge-coupled device camera was dramatically reduced. This signal could be rapidly restored to pre-castration levels after androgen administration. Androgen-induced luciferase activity subsided to nearly basal levels 5 days following the last injection. These data demonstrate that a bioluminescent mouse model with luciferase activity restricted to the prostate gland under the control of a (sPSA) promoter can be used on a real-time basis in live animals to investigate the development and responsiveness of the prostate gland to exogenously administered androgen. This model can be extended to detect the responsiveness of the prostate gland to therapy and used as a founder strain to visualize tumors in hosts with different genetic backgrounds.