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The EMSS laboratory offers established GEM models to investigate prevention, intervention and regression studies. The EMSS offers in vivo cancer models in Breast, Colon and Pancreatic cancer plus other GEM models which can be implanted with the wide variety of human cancer cell lines. The EMSS is able to complete experiments in any established GEM model and to create new GEM models using established lines.
Any procedures that can be performed in xenograft mice, can also be performed in GEM models.
In addition, the EMSS offers full-service colony management of GEM models. The EMSS can perform all breeding, weaning, identification and genotyping services, including backcrossing onto a new genetic background. We are also able to performed timed pregnancy matings and subsequent plug checking. Mice are generally dual identified by ear notching and ear tagging at the time of weaning. A tail snip is also collected at this time for genotyping analysis. Records will be maintained at the EMSS and provided to the investigator in weekly updates. Mice will be put on study at the appropriate age for the experimental design; the EMSS will take care of any paperwork to transfer the mice.
The EMSS can also help complete paperwork for import/export of mice from/to other institutions.
Please note: Experiments using GEM models often take longer to complete than xenograft models because the study must be filled as animals of appropriate genotype become available. This can affect other aspects of the experimental design. Contact the EMSS to discuss any questions or concerns about GEM model studies.
Colonies are kept in maintenance mode and require several weeks lead time to increase production for experimental availability.
Genetic Model Type
Mouse mammary tumors can become palpable at 5-6 weeks and visible at 8-12 weeks. By 14 weeks, metastasis to lungs and bone can occur. Mice are maintained on the FVB background by breeding carrier males to wild type females.
Mice develop multiple benign tumors mostly in the small intestine (on average 40 per mouse) and a few colonic tumors (1-3 per mouse) and usually die by 120 days of age from bowel obstruction. ApcMin/+ mice may develop anemia and females mice may spontaneously develop mammary tumors. These mice are maintained on the C57/BL6/J background by breeding heterozygote males to wild type females (homozygote ApcMin/+ mice are not viable).
These mice carry a latent point-mutant allele of oncogenic K-ras2 (K-rasG12D). Cre-mediated recombination leads to deletion of a transcriptional termination sequence (Lox-Stop-Lox) and expression of the oncogenic protein. By crossing to a tissue-specific cre, you can generate any tissue lung specific model, including lung models (Promoter) and pancreas model (P48-cre). The lung model was established in the Jacks lab (ref.) in 2001, and the pancreas model was published in the Tuveson lab (ref.) in 2003. It is a useful GEM model that allows one to characterize stages of ras-dependent tumor progression.
Cre recombinase induces the release of genes that are floxed. Pdx-1-Cre mice exhibit a stochastic pattern of high-level Cre expression in the pancreas (Hingorani et al., 2003). When combined with Tyler Jacks' latent activatable K-ras allele, LSL-KrasG12D (Kras2, MMHCC strain code 01XJ6), Pdx-1-Cre causes ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs). Some of these lesions progress to invasive and metastatic adenocarcinomas. These mice are currently on a B6.FVB background and are being backcrossed further onto the B6 background.
Villin-cre ER T2
|The Vil-cre is inducible with tamoxifen, usually administered IP for five consecutive days at a concentration of 10 mg/ml. The cre is normally induced at 5 weeks of age, with or without a booster when the mice are older. These mice are maintained on a Bl6 background.|
|These mice are available with collaboration.|
Transgenic Triple Mutant
|These triple mutant mice carry the pdx-cre and B6.129 Kras mutations described above, along with a luciferase mutation that allows for bioluminescent imaging of pancreatic lesions with the administration of luciferin. Triple mutant mice start showing lesions at 20 weeks of age. They are maintained on a mixed Bl6.129 background.|
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