Genetically engineered mice serve as a powerful tool for studying the molecular genetic basis of human cancer and for testing new cancer therapies. The main purpose of the Transgenic and Gene Targeted Mouse Shared Resource (TGTMSR) is to generate genetically altered mice for all Mayo Clinic investigators. The TGTMSR provides two main services, the generation of gene-targeted mice and the production of transgenic animals. The gene targeting service was established in 1999, while the transgenic service is a new service established in 2006 and included in this application for support. Services are very comprehensive allowing investigators with little or no prior experience in generating transgenics or knockouts to implement genetically altered mice into their research programs. We design and purify transgenic DNA constructs and inject these into fertilized eggs. We generate transgenic founders from these eggs and cross these mice to wildtype mice to transmit the transgene through the germline. Furthermore, we design gene targeting vectors (to generate classical or conditional knockouts, hypomorphic alleles or to introduce point mutations in endogenous genes), electroporate these into ES cells and screen for clones carrying the desired alteration by southern blotting. Correctly targeted clones are karyotyped and injected into host blastocysts. Chimeric males are bred to wildtype females to establish germline transmission of the targeted mutation. Our success rate of generating transgenics is thus far 100%, while that of gene targeting is >95%. All users over the current funding period have been Mayo Clinic Cancer Center (MCCC) members. Studies using mouse models generated by the TGTMSR have led to a series of scientific publications over the past 5 years, several of which were in outstanding scientific journals. A total of 27 grant applications supported by the TGTMSR were funded, 13 of which were from the NCI.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Mayo Clinic, Rochester
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Basch, Ethan; Rogak, Lauren J; Dueck, Amylou C (2016) Methods for Implementing and Reporting Patient-reported Outcome (PRO) Measures of Symptomatic Adverse Events in Cancer Clinical Trials. Clin Ther 38:821-30
Renner, Danielle N; Malo, Courtney S; Jin, Fang et al. (2016) Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model. Neurotherapeutics 13:226-36
Navari, Rudolph M; Qin, Rui; Ruddy, Kathryn J et al. (2016) Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med 375:134-42
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Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C et al. (2016) Assessing the genetic architecture of epithelial ovarian cancer histological subtypes. Hum Genet 135:741-56
Ye, Zi; Austin, Erin; Schaid, Daniel J et al. (2016) A multi-locus genetic risk score for abdominal aortic aneurysm. Atherosclerosis 246:274-9
McCormack, Valerie A; Burton, Anya; dos-Santos-Silva, Isabel et al. (2016) International Consortium on Mammographic Density: Methodology and population diversity captured across 22 countries. Cancer Epidemiol 40:141-51
Basal, E; Ayeni, T; Zhang, Q et al. (2016) Patterns of Müllerian Inhibiting Substance Type II and Candidate Type I Receptors in Epithelial Ovarian Cancer. Curr Mol Med 16:222-31
Vaidhyanathan, Shruthi; Wilken-Resman, Brynna; Ma, Daniel J et al. (2016) Factors Influencing the Central Nervous System Distribution of a Novel Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GSK2126458: Implications for Overcoming Resistance with Combination Therapy for Melanoma Brain Metastases. J Pharmacol Exp Ther 356:251-9
Yoon, H H; Foster, N R; Meyers, J P et al. (2016) Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance). Ann Oncol 27:339-44

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