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Model Characteristics - Model:
PB-Hi-myc (ARR2PB-Myc-PAI) / PB-hepsin
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| Model Descriptor |
PB-Hi-myc (ARR2PB-Myc-PAI) / PB-hepsin
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| Official Nomenclature |
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
50% FVB / 50%C57BL/6
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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 |
Both of these models were generated by utilizing the probasin promoter (ARR2PB) sequence to target the myc and hepsin geens to the mouse prostate. The ARR2PB sequence consists of the original probasin sequence PB (-286/+28) combined with an additional androgen response region (Zhang, et al., Endocrinology 2000; 141:4698). The derivation of the PB-Hi-myc (ARR2PB-Myc-PAI) model is described in Ellwood-Yen, et al., Cancer Cell 2003; 4:223. The derivation of the PB-hepsin model is described in Klezovitch, et al., Cancer Cell 2004; 6:185. PB-hepsin and PB-Hi-myc mice were maintained in CF7BL/6J and FVB backgrounds, respectively. All the mice were F1 offspring so the PB-Hi-myc mice were age matched and genetically matched to the hepsin/myc mice, therefore the Pb-Hi-myc and hepsin/myc bigenic mice were 50% C57BL/6J and 50% FVB.
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| Phenotype |
To investigate the effect of hepsin over-expression in a mouse model of prostate adenocarcinoma, they generated the hepsin/myc bigenic mouse. Hepsin upregulation in the myc model accelerates the incidence of adenocarcinoma from 6 to 4.5months. As mice were aged up to 17 months, the prostate tumors of hepsin/myc mice displayed a higher pathological grade of cancer when compared to age-matched mice expressing myc alone in the prostate. This suggests that increased hepsin
expression and activity is important for progression of adenocarcinoma. The tumors in the bigenic mice did not develop features of neuroendocrine (NE) differentiation and were negative for synaptophysin, a NE marker. Further, endogenous hepsin levels, although low when compared to the probasin targeted hepsin, were present in the myc mice and increased significantly (P<0.05) as the myc tumors progressed to 12, 15, and 17 months when compared with the 6-month myc tumor. This finding demonstrates that expression of hepsin in the myc tumors occurs spontaneously and reflects similar events seen during the progression of human prostate cancer. No metastasis was detected in either myc alone or hepsin/myc bigenic mice. It may be hepsin may play an important role in the primary tumors by degrading basement membrane molecules. The low levels of hepsin in the metastatic lesions and metastasis-derived human prostate cell lines indicates a paradoxical nature of hepsin as a metastasis promoting gene.
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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 |
Curator, caMOD
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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 |
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