Department of Veterinary Pathobiology

Craig L. Franklin
Professor

Building Address:  N128 Discovery Ridge Building
Phone Number:(573) 882-6623
Email: franklinc@missouri.edu

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 Complex Microbiota Targeted Rederivation (CMTR), a process where rodents of the desired genotype are rederived using embryo transfer into surrogate dams with one or more desired GM profiles.  The pups are then seeded with the GM of their respective surrogate dams, resulting in genetically identical animals with different, defined, complex GM.  Concurrently, we are evaluating other means to manipulate GM 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, neonatal immunity, autism and aging.

 

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 113 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. Feb 12;10(2):e0116704, 2015 PMCID PMC25675094.

Lloyd, K, C. Franklin, C. Lutz and T. Magnuson. Reproducibility: Use Biobanks or Lose Them. Nature 522:151-153, 2015, PMID 26062496 (Comment; PMCID not applicable)

Ericsson, A.C., D.J. Davis, C.L. Franklin and C.E. Hagan. Exoelectrogenic Capacity of Host Microbiota Predicts Lymphocyte Recruitment to the Gut. Physiol Genomics 47:243-252, 2015, PMID 25852170; PMCID PMC4491528 (available 7/1/16)

Ericsson, A.C., C.L. Franklin. (invited review) Manipulating the Gut Microbiota: Methods and Challenges. ILAR J 56(2):205-17, 2015. PMID 26323630. PMCID:PMC4554251 (Available 8/31/16)

Ericsson, A.C., C.L. Franklin. Isolation of Segmented Filamentous Bacteria from a Complex Gut Microbiota. BioTechniques 59(2):94-98, 2015. PMID 26260088; PMCID in progress

Ray, A., S. Basu, R.Z. Gharaibeh, L.C. Cook, R. Kumar, E.J. Lefkowitz, C.D. Morow, C.L. Franklin, T.L. Geiger, N. Salzman, A. Fodor, and B.N. Dittel. Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cell Development in the Absence of IL-10 Signaling in Macrophages. J Immunol 195(7):3071-85, 2015. PMID 26324769; PMCID in progress.

Ericsson, A.C., S. Akter, M.M. Hanson, S.B. Busi, T.W. Parker, R.J. Schehr, M.A. Hankins, C.A. Ahner, J.W. Davis, C.L. Franklin, J.M. Amos-Landgraf, E.C. Bryda. Differential Susceptibility to Colorectal Cancer Due to Naturally Occurring Gut Microbiota. Oncotarget 6(32):33689-704. PMID 26378041; PMCID in progress.

Miller, P.G., M.B. Bonn, C.L. Franklin, A.C. Ericsson, and S.C. McKarns. TNFR2 Deficiency Acts in Concert with Gut Microbiota to Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease.  J Immunol 195(10):4668-4684, 2015. PMID 26475926; PMCID in progress.

Alvarado, C.G., A.G. Kocsis, M.L. Hart, M.J. Crim, M.H. Myles and C.L. Franklin. Pathogenicity of Helicobacter ganmani Infection in Mice Susceptible and Resistant to Infection with H. hepaticus. Comp Med 65(1):15-22, 2015.  PMID 25730753 PMCID in process.

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

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

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

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.

 

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