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.

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?GEMM

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

Breast Cancer

  1. 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.
  2. 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.
  3. MMTV-Neu - This model represents HER2 positive breast cancer tumors. This is a murine model that overexpresses the rat analog to HER2.


  1. 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.
  2. 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.
  3. 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.


  1. The K18-gT121+/-; p53fl/fl; Brca1fl/fl mouse model is a unique serous ovarian cancer genetically engineered mouse model that specifically and somatically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial (OSE) cells (KpB mouse model) (Szabova et. al., Pertrubation of Rb, p53, and Brca1 or Brca1 cooperate inducing metatstatic serous epithelial ovarian cancer, Cancer Research, 2012, 72: 4141-4153). Inactivation of all 3 Rb proteins by T121 (a fragment of the SV40 large T antigen) is driven by the keratin 18 (K18) promoter. Expression of the T121 transgene and knockout p53 and Brca1 are conditional and only activated via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice. Within 3 months post induction, ovarian carcinoma in situ is present within the injected ovary. At 4-6 months, tumors develop in the affected ovary, while the un-injected ovary remains normal and can be used as a contralateral control. Histologic examination and marker studies demonstrate that the KpB ovarian tumors recapitulate the major features of serous ovarian cancer tumors, the histologic subtype that is most common in women. It has been recently reported through The Tumor Cancer Genome Atlas (TCGA) project that RB1, p53 and BRCA1 are central to the pathogenesis of serous ovarian cancer in patients, which further supports the relevance of this novel model.