Research emphasis: The overall goal of our laboratory is to support the needs of the Mutant Mouse and Rat Resource and Research Centers and biomedical community by performing research to understand how differing complex microbiota modulate animal models of disease and developing means to manipulate microbiota to ensure reproducibility of models being distributed.
The Mutant Mouse Resource and Research Center (MMRRC) and Rat Resource and Research Center (RRRC) at the University of Missouri (MU) are unique NIH-funded repositories that import, store and distribute a vast number of mutant mouse and rat strains and embryonic stem cells. Genetically-engineered rodents (i.e., transgenics, knock-outs and knock-ins) are invaluable to almost all fields of medicine. Tens of thousands have been created over the last two decades to facilitate better understanding of developmental biology and disease and to test and improve the function of drugs and therapeutics. The specific aims of the MMRRC and RRRC are to 1) provide biomedical investigators with the rodent models and related reagents they require for their research, 2) provide value-added services to aid the biomedical research community, and 3) perform research that has broad application to all models distributed. Services include cryopreservation, cryoresuscitation from embryos or sperm, rederivation, genotyping and assay development, marker-assisted genetic analysis for development of speed congenics, karyotyping, colony management, phenotyping, and microbiome analysis.
Microbiota Research. There is abundant evidence that the composition of the gut microbiota (GM) has a strong influence on phenotypes of rodent models of disease. This is of particular concern in the context of rederivation, as cryopreserved rodents will acquire the GM of their respective surrogate dam at birth, rather than the GM that was present in the ancestral line. Moreover, abundant anecdote and emerging data suggest that factors in the rodent’s environment may influenced development and composition of GM. With this in mind, the MU Metagenomics Laboratory is characterizing the effect of several variables (e.g. housing, diet, genetic background) on the GM of laboratory rodents, to provide users of the MMRRC and RRRC empirical evidence regarding the impact of these and other factors. We are also evaluating practical means for users to manipulate the GM of rederived rodents to a desired composition, including breeding to and co-housing with rodents harboring the desired GM and transfer of GM via gastric fecal microbiota transfer. Last, we are assessing the impact of differing GM on two common models of disease: the IL-10 knockout model of inflammatory bowel disease and the viable yellow model of epigenetics.
We also participate in several collaborative projects that involve the study of rodent models of human disease. The latter include studies on multiple sclerosis, diabetes, asthma and neonatal immunity.
Teaching Responsibilities: Basic and Advanced Immunology, Pathology of Laboratory Animals, Laboratory Animal Medicine, Grant and Manuscript Writing for Biomedical Researchers, Foundations in Veterinary Research and Discovery, Communication, Collaboration and Conflict Resolution
Selected Publications (from 105 total):
Ericsson, A.C., J.W. Davis, W. Spollen, N. Bivens, S. Givan, C.E. Hagan, M. McIntosh and C.L. Franklin. Effects of Genetic Background on the Composition of the Gut Microbiota of Inbred Mice. PLOS ONE (in press)
Alvarado, C.G., A.G. Kocsis, M.L. Hart, M.J. Cri, M.H. Myles and C.L. Franklin. Pathogenicity of Helicobacter ganmani Infection in Helicobacter Susceptible and Resistant Mice. Comp Med (in press).
Ericsson, A.C., C.E. Hagan, D.J. Davis, and C.L. Franklin. Segmented Filamentous Bacteria: Commensal Microbes with Potential Effects on Research. Comp Med 64:90-8, 2014. PMCID PMC3997285.
Cook, L.C., A.E. Hillhouse, M.H. Myles, D.B. Lubahn, E.C. Bryda, J.W. Davis and C.L. Franklin. The Role of Estrogen Signaling in a Mouse Model of Inflammatory Bowel Disease. PLOS ONE 9(4):e94209, 2014. PMCID PMC3978010
Lee, K., D.N. Kwon, T. Ezashi, Y.J. Choi, C. Park, A.C. Ericsson, A.N. Brown, M.S. Samuel, K.W. Park, E.M. Walters, J.H Kim, C.L. Franklin, C.N. Murphy, R.M. Roberts, R.S. Prather and J-H. Kim. Engraftment of human iPS and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency. PNAS 111(30):7260-5, 2014. PMCID PMC4034252.
Gubin, M.M., P. Techasintana, J.D. Magee, G.M. Dahn, R. Calaluce, J.L. Martindale, M.S. Whitney, C.L. Franklin, C. Besch-Williford, J.W. Hollingsworth, K. Abdelmohsen, M. Gorospe, and U. Atasoy. Conditional Knockout of the RNA-Binding Protein HuR in CD4(+) T Cells Reveals a Gene Dosage Effect on Cytokine Production. Mol Med 20(1):93-108, 2014. PMCID PMC3960399
Ericsson, A.C., M.J. Crim and C.L. Franklin. A Brief History of Animal Modeling. Mo Med 110(3):201-5, 2013. PMCID PMC23829102
Franklin, C.L. One Medicine: Collaborative Research on Human & Animal Disease for the Betterment of Both. Mo Med 110(3):195-6, 2013.
McCoy, A., C.L. Besch-Williford, C.L. Franklin, E.J. Weinstein, and X. Cui. Creation and Characterization of a Tp53 Knockout Rat. Dis Mod Mech 61(1):269-78, 2012. PMCID PMC3529357
Donahue, L.R., M. Hrabe de Angelis, M. Hagn, C. Franklin, K.C.K. Lloyd, T. Magnuson, C. McKerlie, N. Nakagata, Y. Obata, S. Read, W. Wurst, A. Hörlein, and M.T. Davisson. Centralized Mouse Repositories. Mamm Genome 23(9):559-71, 2012. PMCID PMC3709583
Livingston, R.S., C.L. Besch-Williford, M.H. Myles, C.L. Franklin, M.J. Crim and L.K. Riley. Pneumocystis carinii infection causes lung lesions historically attributed to rat respiratory virus. Comp Med 61(1):1-8, 2011. PMCID PMC3060427
Hillhouse, A., J. Taylor, E. Bryda, M. Myles and C. Franklin. Quantitative trait loci in a bacterially induced model of inflammatory bowel disease. Mamm Genome 22:544-555, 2011. PMCID PMC3804127
Roberts-Pilgrim, A., E. Makareeva, M.H. Myles, C.L. Besch-Williford, A.C. Brodeur, A.M. Walker, S. Liekin, C.L. Franklin, and C. Phillips. Deficient degradation of homotrimeric type I collagen [a1(I)3] glomerulopathy in oim mice. Mol Genet Metab 104:373-382, 2011. PMCID PMC3205245
Stellato, C. M.M. Gubin, J.D. Magee, X. Fang, J. Fan, V. Casolaro, D.M. Tartar, J. Chen, G.A. Jackson, C. Franklin and U. Atasoy. Coordinate regulation of GATA3 and Th2 cytokine gene expression by the RNA-binding protein HuR. J Immunol 187(1):441-9, 2011. PMID21613615
Divekar, R., C. Haymaker, J Cascio, F. Guloglu, J. Ellis, D. Tartar, C. Hoeman, C. Franklin, B. Zinselmeyer, J. Lynch, M. Miller and H. Zaghouani. T Cell Dynamics During Induction of Tolerance and Suppression of Experimental Allergic Encephalomyelitis. J Immunol 187(8):3979-86, 2011. PMCID PMC3186833
Patten, C.C., M.M. Myles, C. L. Franklin and R.S. Livingston. Cytokine perturbations in the laboratory mouse after Pasteurella pneumotropica inoculation. Comp Med 60(1):18-24, 2010. PMCID PMC286080
Ericsson, A., M. Myles, W. Davis, L. Ma, M. Lewis, L. Maggio-Price and C. Franklin. Non-invasive detection of inflammation-associated colon cancer in a mouse model. Neoplasia 12:1054-1065. (featured article), 2010. PMCID PMC3003140
Walters, E., B. Bauer., C. Franklin, T. Evans, E. Bryda, L. Riley., and JK. Critser. Mutational insertion of a ROSA26-EGFP transgene leads to spermiogenesis defects and male infertility in mice. Comp Med 59(6):545-552, 2009. PMCID PMC2798843
Jain, R., D.M. Tartar, R.K. Gregg, R. Divekar, J.J. Bell, H. Lee, P, Yu, J.S. Ellis, C.M. Hoeman, C.L. Franklin and H. Zaghouani. Innocuous IFN induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J Exp Med 205(1):207-218, 2008. PMCID PMC2234380
Besselsen, D.G., C.L. Franklin, R.S. Livingston and L.K. Riley (invited review). Lurking in the shadows: emerging rodent infectious diseases. ILAR J 49(3):277-290, 2008. PMCID PMC3804110
Wiedmeyer, C.E., D. Ruben, and C Franklin. Complete blood count, clinical chemistry and serology profiles using a single tube of whole blood from mice. J Amer Assoc Lab Anim Sci 46:59-64, 2007.
Bauer, B.A., S. Boedges, C.R. Cook, E.C. Bryda and C.L. Franklin. Breeding Colony Refinement through Phenotypic and Genotypic Characterization of the SPRD-Pkdr1/Rrrc Rat Model of Polycystic Kidney Disease. Comp Med 57:190-196, 2007.
Brodeur, A.C., D.A. Wirth, C.L. Franklin, L.W. Reneker, J.H. Miner, and C.L. Phillips. Type I Collagen Glomerulopathy: Postnatal initiation of homotrimeric collagen deposition follows glomerular maturation. Kid Internat 71(10):985-93, 2007.
Myles, M.H., B.K. Dieckgraefe, J.M. Criley and C.L. Franklin. Characterization of cecal gene expression in a differentially susceptible mouse model of bacterial-induced inflammatory bowel disease. IBD 13(7): 822-36., 2007
Franklin, C. (invited review). Comparative Medicine: A review for clinicians. Missouri Med 104(6)517-521, 2007.
Franklin, C.L. (invited review) Microbial considerations in genetically-engineered mouse research. ILAR J 47(2):140-154, 2006.