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Model Characteristics - Model:
12T-7s
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| Model Descriptor |
12T-7s
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| Official Nomenclature |
CD-1-Tg(Tag)12T7sRjm
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
CD-1
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| Is This a Tool Strain? |
No
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Developmental Stage
(applies only to Zebrafish) |
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| Experimental Design |
In the LPB-Tag models, the large probasin (LPB) promoter has been used to target expression of the SV 40 large T antigen (Tag) oncogene which has a deletion in the SV40 early region removes expression of the small t antigen. The expression of the Tag gene will inactivate both the pRB and the p53 tumor suppressor genes. This is substantially different from the TRAMP line that expresses not only the Large T but also the small t antigen. The small t antigen inhibits protein phosphatase 2A and activates the cyclin D promoter resulting in changes in MAPK and SAPK pathways, respectively.
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| Phenotype |
The 12T-7 line diverged into two sublines termed 12T-7f (fast growing) and 12T-7s (slow growing) prostate tumors. The 12T-7f males are infertile by 8 weeks while 12T-7s males can be used as breeders. The 12T-7s line develops large prostate tumors by 15-20 weeks of age. At this stage, the majority of the prostate is composed of high grade prostatic intraepithelial neoplasia (HGPIN).
A general characterization of all LPBTag lines including pathology, immunohistochemistry and hormonal regulation indicates that these tumors are similar to stages seen in human prostatic disease. Initially, multifocal proliferating lesions were detected in the prostatic epithelium, starting as low-grade dysplasia. Reactive stromal proliferation was induced and continued to develop throughout the progression to high-grade dysplasia, carcinoma in situ, and adenocarcinoma. Epithelial cell transformation was accompanied by the down-regulation of differentiated function, as suggested by the loss of dorsolateral prostate-specific secretory proteins. By immunohistochemistry, the prostatic epithelium was shown to express Tag, androgen receptor (AR), cytokeratin, and proliferating cell nuclear antigen. Six of the transgenic lines have androgen-dependent since tumors regressed in castrated animals. Using MRI to monitor prostate tumor size, 74% of the tumors that regressed after castration and began to regrow 2-6 months post-castration. The regrowing primary tumors varied in pathology but many developed high grade neuroendocrine carcinoma that expresses Tag with decreased AR expression and areas of high grade dysplasia that continues to proliferate, loses Tag expression but continue to expression AR. After primary tumor regrowth, a majority of the mice showed metastatic lesions that express neuroendocrine markers.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
Male Only
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| Submitted by |
Matusik, Robert
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| Principal Investigator / Lab |
Matusik, Robert
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| Comment |
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| Model Availability: This model is available from |
| Strain |
Distributor |
Stock number |
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