Generation of transgenic mouse models for the development of...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A01K 67/027 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01) C12N 15/10 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2357181

The utility of the promoter/enhancer region (i.e. regulatory region) of the PSP94 gene in targeting expression of heterologous genes, to the prostate gland was analyzed. Three breeding lines (i.e., line A, line B line C) of the PSP-TGMAP (PSP94 gene driven transgenic mouse of adenocarcinoma of the prostate) model were established with constructs containing regulatory regions with or without additional exon/intron sequence of the PSP94 gene. These regulatory regions were operatively linked to the simian virus 40 (SV40) T antigen (Tag, including both the large T and small t antigens). Histopathology evaluation of tumor grade, transgene expression, tumor responsiveness to androgen deprivation and tumor metastatic potential were analyzed and reported herein. This study indicates that regulatory regions (i.e. the promoter/enhancer with exon/intron region) of the PSP94 gene efficiently target the expression of heterologous genes to prostate tissue. Furthermore, the PSP-TGMAP model provides a valuable tool for the analysis of prostate cancer development and for developing new gene therapy vector for the treatment of prostate cancer. Based on this study, mouse PSP94 promoter/enhancer (i.e., regulatory) region may be used in the generation of a "shuttle vector" fit for prostate targeting in both mouse CaP model and in human clinical trial.

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