Reference SummaryPoliti K, Oncogene 2004 Feb 26;23(8):1558-65
Title |
'Designer' tumors in mice. |
Authors |
Politi K; Kljuic A; Szabolcs M; Fisher P; Ludwig T; Efstratiadis A |
Journal |
Oncogene |
Volume |
23 |
Issue |
8 |
Year |
2004 |
Pages |
1558-65 |
Abstract |
We have developed and tested successfully a general method based on Cre-mediated recombination that can be used for ubiquitous or tissue-specific expression of protein products, including tumor-inducing oncoproteins. Depending on the specificity of a chosen promoter driving cre expression, tumors develop by design in bitransgenic mouse progeny derived by crossing Cre-producing mice with partners carrying a dormant oncogenic transgene (targeted into the 3' noncoding region of the cytoplasmic beta-actin locus) that becomes functional after excision of a 'floxed' DNA segment. To provide proof-of-principle, we have used as models transgenes encoding the polyomavirus middle T antigen (PVMT) and the T antigens of the SV40 early region (SVER). Cre-dependent activation of widespread SVER expression resulted in hyperplasias or invasive tumors affecting particular visceral smooth muscles, whereas Cre-dependent, mammary gland-specific expression of PVMT-induced adenocarcinomas, according to plan. Unexpectedly, we also encountered spontaneous (Cre-independent) oncogene expression occurring as a rare event, which simulates the initiation of sporadic tumors and leads to PVMT-induced hemangiomas and mammary carcinomas or SVER-induced disseminated sarcomas, thus, revealing particular tissue susceptibilities to the actions of these oncoproteins. |
Links |
J:87544 – MGI References 14661057 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| B6;129S1-Actbtm1(PyVT)Arge/+ Waptm1(cre)Arge/+ | Blood vessel hemangioma | Blood vessel |
70.58 - 96.97 |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangioma | Blood vessel |
50.48 - 100 |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangioma | Lung |
observed |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangioma | Liver |
observed |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangioma | Uterus |
observed |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangioma - cavernous | Blood vessel |
very high |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangioma - sclerosing | Blood vessel |
observed |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Blood vessel hemangiosarcoma | Lung |
8.33 |
||
| B6;129S1-Actbtm1(PyVT)Arge/+ Waptm1(cre)Arge/+ | Liver carcinoma - undifferentiated | Liver |
2 - 3.03 |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Mammary gland adenocarcinoma | Mammary gland |
75 |
||
| B6;129S1-Actbtm1(PyVT)Arge/+ Waptm1(cre)Arge/+ | Mammary gland adenocarcinoma - intraductal | Mammary gland |
30 - 88.24 |
||
| 129S1/Sv-Actbtm1(PyVT)Arge/+ | Mammary gland adenofibroma | Mammary gland |
8.33 |
||
| 129S1-Actbtm2(Tag)Arge | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
high |
||
| 129S1-Actbtm2(Tag)Arge | Mesodermal cell/mesoblast sarcoma - undifferentiated | Mesodermal cell/mesoblast |
100 |
||
| 129S1-Actbtm2(Tag)Arge | Mesodermal cell/mesoblast sarcoma - undifferentiated | Liver |
high |
||
| 129S1-Actbtm2(Tag)Arge | Mesodermal cell/mesoblast sarcoma - undifferentiated | Spleen |
high |
||
| 129S1-Actbtm2(Tag)Arge | Mesodermal cell/mesoblast sarcoma - undifferentiated | Thoracic cavity |
high |
||
| 129S1-Actbtm2(Tag)Arge/+ | Mesodermal cell/mesoblast sarcoma - undifferentiated | Mesodermal cell/mesoblast |
high - 100 |
||
| 129S1-Actbtm2(Tag)Arge/+ | Mesodermal cell/mesoblast sarcoma - undifferentiated | Liver |
high |
||
| 129S1-Actbtm2(Tag)Arge/+ | Mesodermal cell/mesoblast sarcoma - undifferentiated | Spleen |
high |
||
| 129S1-Actbtm2(Tag)Arge/+ | Mesodermal cell/mesoblast sarcoma - undifferentiated | Thoracic cavity |
high |
||
| B6;129S1-Actbtm1(PyVT)Arge/+ Waptm1(cre)Arge/+ | Spleen carcinoma - undifferentiated | Spleen |
2 - 3.03 |
||
| B6;129S1-Actbtm1(PyVT)Arge/+ Waptm1(cre)Arge/+ | (Unspecified organ) tumor | (Unspecified organ) |
100 |