A new transgenic mouse model (called PB-cre), in which cre recombinase is expressed specifically in the male prostate under the control of the prostate-specific probasin promoter, has been derived for the study of prostate development and cancer. In this R2l application, we first propose to characterize the expression pattern of this transgene and to define the onset and extent of recombination over time of conditional genes. We then propose to selectively mutate the retinoid receptor RXR alpha: gene in prostatic epithelium in normal mice and in mice genetically disposed to prostatic epithelial dysplasia.
Specific Aim 1 : To define the pattern of recombination driven by the PB- cre transgene. A comprehensive description of the timing and extent of recombination as driven by this transgene will be obtained by crossing to the well-characterized conditional reporter gene ROSA26R (R26R).
Specific Aim 2 : To selectively mutate the RXR alpha: gene in prostate epithelium. Abundant prior and new evidence presented in this proposal implicate a role for retinoids and retinoid receptors, particularly RXR alpha:, in the derivation and maintenance of prostatic epithelium and in the progression of prostate cancer. We will cross the crc-expressing transgene with a conditional allele of RXR alpha:, and evaluate the nature and extent of morphological alterations in the prostatic epithelium. We will also cross the conditional mutation of RXR alpha: into the Nkx3. l knockout mouse model to evaluate the extent to which RXR alpha: modulates the initiation and progression of prostate dysplasia and cancer.
| Huang, Jiapeng; Powell, William C; Khodavirdi, Ani C et al. (2002) Prostatic intraepithelial neoplasia in mice with conditional disruption of the retinoid X receptor alpha allele in the prostate epithelium. Cancer Res 62:4812-9 |
| Wu, X; Wu, J; Huang, J et al. (2001) Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech Dev 101:61-9 |
