The Mouse Phase 1 Unit at UNC - Chapel Hill currently maintains a standing colony of over 2,000 cages producing three models of breast cancer, three models of melanoma and two models of lymphoma/leukemia. More models are in the development stage including additional models of breast cancer, melanoma, bladder, ovarian, and lung cancer.
What are GEMMs?
Genetically Engineered Mouse Models are transgenic animals in which gene knock-out and knock-in technologies have made it possible for us to more faithfully mimic the genetic and biological evolution of human cancers. Our GEMMs develop spontaneous, autochthonous tumors and have the microenvironment required for tumor progression, including degradation of the matrix and angiogenesis. Genetically Engineered Mouse Models offer many advantages over xenograft models. On top of spontaneous, autochthonous tumors, GEMMs can be engineered to have a short latency yet with high penetrance. Also, in contrast with xenografts, GEMMs are immuno-competent animals.
Our Current Models
- C3(1)/Tag - This model is similar to the human basal disease as shown by gene expression analysis and is one of two triple-negative breast cancer GEMMS used by the MP1U. The C3(1)/Tag expresses Simian Virus 40 large T antigen shown to inactivate both p53 and RB. Large T-antigen binds and inactivates the RB and p53 tumor suppressor genes, explaining why this model is a faithful recapitulation of human basal breast cancer, which also harbors RB and p53 inactivation. This model is also shown to have frequent K-Ras amplification and infrequent Ras mutations.
- T11 - This model represents the claudin-low subtype of human tumors recently described by Dr. Charles Perou. A subset of the Triple-negative phenotype (ER-, PR-, HER2-), these tumors are seen in 15% of all human breast cases. They are highly refractory to chemotherapy and offer a much worse prognosis for the patient. This model, driven by p53 loss, is an orthotopic serial injection derived from balb/c animals.
- MMTV-Neu - This model represents HER2 positive breast cancer tumors. This is a murine model that overexpresses the rat analog to HER2.
- Tyrosine-Hras/Ink/Arf null (TRIA) - First developed by Dr. Lynda Chin, this RAS-driven model of melanoma lacks Ink/Arf signaling, a key event in melanoma development. Ras events are linked to greater than 70% of all melanomas. This model offers a rational approach to studying efficacy in immunocompetent autochonous tumors. This model faithfully demonstrates overall response rates to standard of care chemotherapy when compared to human trials.
- Pten/Braf - This is melanoma model developed by Dr. Marcus Bosenberg, combines the expression of BrafV600E with Pten loss that is consistent with human melanoma genetic profiles. About 20% of human melanoma has a combination of mutated Braf and the silencing of Pten expression.
- LKB1 - LKB1 inactivation with K-Ras activation in the melanocytes of mice has produced a highly metastatic melanoma with 100% penetrance. Somatic LKB1 mutations, like in our murine model, occur in 10% of cutaneous melanoma.
Lymphoma & Leukemia
- Eµ-myc - this model was first developed in 1985, the mouse over expresses mouse myc in B cell, causing increased pre-B cells in the bone marrow throughout life and spontaneous pre-B and B cell lymphomas starting around 12 weeks of age. This model has a dichotomy, where about 50% of the mice get early tumors, before 20 weeks and the rest may get later tumors. This model is currently being further characterized to learn more about the illness’s dichotomy and to include a reporter allele to catch illness at an earlier stage.
- PTen LCK Cre - These mice harbor a Pten deficiency in CD4 expressing T cell and develops T cell lymphoma.