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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA015083-39
Application #
8465663
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
39
Fiscal Year
2013
Total Cost
$131,585
Indirect Cost
$40,490
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Wallace, Sumer K; Halverson, Jessica W; Jankowski, Christopher J et al. (2018) Optimizing Blood Transfusion Practices Through Bundled Intervention Implementation in Patients With Gynecologic Cancer Undergoing Laparotomy. Obstet Gynecol 131:891-898
Shrestha, Shikshya; Zhang, Cheng; Jerde, Calvin R et al. (2018) Gene-Specific Variant Classifier (DPYD-Varifier) to Identify Deleterious Alleles of Dihydropyrimidine Dehydrogenase. Clin Pharmacol Ther 104:709-718
Hu, G; Dasari, S; Asmann, Y W et al. (2018) Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large cell lymphoma. Leukemia 32:565-569
Geller, James I; Fox, Elizabeth; Turpin, Brian K et al. (2018) A study of axitinib, a VEGF receptor tyrosine kinase inhibitor, in children and adolescents with recurrent or refractory solid tumors: A Children's Oncology Group phase 1 and pilot consortium trial (ADVL1315). Cancer 124:4548-4555
Luchtel, Rebecca A; Dasari, Surendra; Oishi, Naoki et al. (2018) Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood 132:1386-1398
Oishi, Naoki; Brody, Garry S; Ketterling, Rhett P et al. (2018) Genetic subtyping of breast implant-associated anaplastic large cell lymphoma. Blood 132:544-547
DuBois, Steven G; Mosse, Yael P; Fox, Elizabeth et al. (2018) Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma. Clin Cancer Res 24:6142-6149
Farber, Benjamin A; Lalazar, Gadi; Simon, Elana P et al. (2018) Non coding RNA analysis in fibrolamellar hepatocellular carcinoma. Oncotarget 9:10211-10227
Lu, Yingchang; Beeghly-Fadiel, Alicia; Wu, Lang et al. (2018) A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk. Cancer Res 78:5419-5430
Dasari, Surendra; Newsom, Sean A; Ehrlicher, Sarah E et al. (2018) Remodeling of skeletal muscle mitochondrial proteome with high-fat diet involves greater changes to ?-oxidation than electron transfer proteins in mice. Am J Physiol Endocrinol Metab 315:E425-E434

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