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Model Characteristics - Model:
TβRII(fl/fl);PY;MC
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| Model Descriptor |
TβRII(fl/fl);PY;MC
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| Official Nomenclature |
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
Not specified
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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 |
Transforming growth factor (TGF)-beta signaling has been associated with early tumor suppression and late tumor progression; however, many of the mechanisms that mediate these processes are not known. Using Cre/LoxP technology, with the whey acidic protein promoter driving transgenic expression of Cre recombinase (WAP-Cre), we have now ablated the type II TGF-beta receptor (T¿RII) expression specifically within mouse mammary alveolar progenitors. Transgenic expression of the polyoma virus middle T antigen, under control of the mouse mammary tumor virus enhancer/promoter, was used to produce mammary tumors in the absence or presence of Cre (T¿RIIsup(fl/fl);PY/sup and T¿RIIsup(fl/fl);PY;WC/sup, respectively).
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| Phenotype |
The loss of TGF-beta signaling significantly decreased tumor latency and increased the rate of pulmonary metastasis. The loss of TGF-beta signaling was significantly correlated with increased tumor size and enhanced carcinoma cell survival.
MMTV-Cre-dependent loss of TβRII in MMTV-PyVmT tumors also significantly decreased tumor latency similar to results from a previous study. The TβRII(fl/fl);PY;MC mice developed palpable tumors at 36 d whereas the TβRII(fl/fl);PY control mice had a median time to tumor palpation of 45 d. Interestingly, when TβRII was deleted using WAP-Cre, palpable tumors were detected earlier than when using MMTV-Cre to mediate deletion. A significant increase in the number of visible metastases occurred in the TβRII(fl/fl);PY;WC and TβRII(fl/fl);PY;MC models when compared with the TβRII(fl/fl);PY controls. Total body weight at the time of sacrifice showed a significant increase in tumor burden associated with the TβRII(fl/fl);PY;WC and TβRII(fl/fl);PY;MC models when compared with TβRII(fl/fl);PY controls.
Together, our current results indicate that loss of TGF-beta signaling in mammary alveolar progenitors may affect tumor initiation, progression, and metastasis through regulation of both intrinsic cell signaling and adjacent stromal-epithelial interactions in vivo.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
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| Submitted by |
caMOD, Curator
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| Principal Investigator / Lab |
Moses*, Harold
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| Comment |
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| Model Availability: This model is available from |
| Strain |
Distributor |
Stock number |
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 Comments (Please login to submit new comments) |
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