Abstract B43: Mouse models for cancer research available from The Jackson Laboratory Repository
Authors: Valenzuela Alicia , Lutz Cathleen M. , Rockwood Stephen F. , Sasner Michael , Donahue Leah Rae 
Published: May 2015

The Jackson Laboratory Repository serves as a centralized facility for the development, rederivation, distribution and cryopreservation of mouse models of human biology and disease. Hundreds of new strains are added annually to one of the largest collections of characterized mouse strains available to the international biomedical research community. This poster features a wide range of models ideally suited to studies related to cellular cancers, solid tumors, and conditional/inducible cancer-associated gene expression.

To highlight transplantation/engraftment and “humanized” mouse research, several mouse lines with improved engraftment and specialized human cell colonization are described. Such animals complement our NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl) and NRG (NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl) mice as ideal tools for engraftment with a wide range of malignant or non-malignant human or mouse tissues or cell lines. Several of the NSG or NRG models are combined with human HLA genes, including: Tg(HLA-DRB1)31Dmz, Tg(HLA-DRA,HLA-DRB1*0401)39-2Kito, Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz, Tg(HLA-A/H2-D/B2M)1Dvs and Tg(HLA-A2.1)1Enge. NSG is also combined with transgenes expressing human cytokines such as Tg(CMV-IL3,CSF2,KITLG)1Eav and Tg(PGK1-KITLG*220)441Daw.

Several new knockout and floxed strains carry genes associated with tumor suppression. Septin 4 (Sept4)-null mice exhibit an increased incidence of hematopoietic malignancies. Tip30 (or Htatip2) knockout mice develop carcinoma and/or sarcoma in a variety of tissues. Floxed genes associated with tumor suppression include Ets2 and Fbxw7. Ets2 (E26 avian leukemia oncogene 2) functions in tumor repressive and tumor supportive roles in different types of cancer and epithelial tumor microenvironments. The ubiquitin ligase, Fbwx7, is involved in targeting the cell cycle regulators c-Myc and NOTCH1 for proteasomal degradation.

Other recent additions include the Cre/Tet-Off microRNA (Mir21 and Mir155) strains under the control of the widely expressed ROSA26 promoter. In this Cre/Tet-Off system, combination with a tissue-specific Cre expressing strain removes a STOP cassette allowing overexpression of the microRNA; doxycycline (dox) administration turns off expression. Overexpression of either mir-21LSL-Tetoff or mir-155LSltTa results in lymphomas, inhibition of expression results in tumor regression. Also notable are two transgenes expressing a tetO-MYC (myelocytomatosis oncogene) and a tetO-Tag (SV40 large T antigen). In double transgenic mice, TetO-MYC; Cebpb-tTA (liver-specific), withdrawal from dox results in invasive metastatic liver tumors. The c-Myc-EFGP mice have a fluorescent reporter knocked into the Myc oncogene; PRCre knockin mice express Cre recombinase in progesterone expressing cells and may be useful for studying progesterone-responsive cells/tissues. The Tet2f/f mouse provides a conditional (floxed) allele of the Tet2 oncogene for the creation of tissue-specific mutants. TET2 is associated with myeloid malignancies in humans.

The Jackson Laboratory Repository maintains a searchable online resource to find mice (JAX® Mice database: www.jaxmice.jax.org/query). Anyone wishing to donate their mouse strains for cryopreservation/distribution may submit them using our online submission form (www.jax.org/donate-a-mouse). The Jackson Laboratory Repository is supported through our NCI designated Cancer Center and other NIH mechanisms, The Howard Hughes Medical Institute, The Ellison Medical Foundation and several private charitable foundations.

Please stop by for a detailed list of recently added mouse strains for cancer research. Also visit our cancer research resources website at: www.jaxmice.jax.org/cancer.

Citation Format: Alicia Valenzuela, Cathleen M. Lutz, Stephen F. Rockwood, Michael Sasner, Leah Rae Donahue. Mouse models for cancer research available from The Jackson Laboratory Repository. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr B43.