The over-arching mission of the Animal Models of inflammatory Disease Core is to support investigators of the Cincinnati Children's Hospital Research Community in the use of experimental animal settings of rheumatic diseases, autoimmune diseases, and inflammatory processes. In so doing, the Core will promote advances in the understanding and treatment of arthritic and auto-inflammatory diseases. Animal models, particularly those involving murine systems, have emerged as powerful tools in arthritis and autoimmune research due to the fact that any gene identified as a candidate "disease modifier" can be easily manipulated in mice through either "gene-targeting" or standard transgenic technologies. In providing an in vivo experimental system amenable to investigator-imposed genetic alterations (e.g., loss-of-function or gain-of function), animal models offer the unique opportunity (not available in human subjects) to test hypotheses focused on identifying the fundamental mechanisms that drive auto-inflammatory disease. Animal models offer the ability of collecting entire tissues (i.e., whole joints) for detailed analyses of biochemical, immunological, pathological and gene expression properties, and as well as performing comprehensive temporal analyses of disease progression. The utility of animal models has been highlighted by the fact that these experimental systems have often provided the early proof-of-principle for some of the most powerful therapeutic strategies (e.g., anti-cytokine therapies such as TNF blockers). Finally, many animal models of arthritis and other auto-inflammatory diseases are available with distinct etiologies (e.g., adaptive immune driven vs. cytokine driven), and thus provide a variety of distinct frameworks to study these complex disease processes.
The Specific Aims of the Animal Models of Inflammatory Diseases Core are to (i) provide technical expertise and starter reagents to investigators interested in animal models of auto-inflammatory disease (i.e., arthritis, neuroinflammatory disease, and dermatomyositis), and (ii) provide material assistance in the generation and characterization of both transgenic and gene-targeted mice that will be instructive with regard to the development and progression of auto-inflammatory disease. This core serves as the perfect complement to ongoing basic and clinical studies (e.g., immunology, informatics, and gene discovery) of the Cincinnati Rheumatic Diseases Core Center Research Base.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR047363-13
Application #
8500201
Study Section
Special Emphasis Panel (ZAR1-MLB)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
13
Fiscal Year
2013
Total Cost
$121,223
Indirect Cost
$41,992
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Raghu, Harini; Jone, Alice; Cruz, Carolina et al. (2014) Plasminogen is a joint-specific positive or negative determinant of arthritis pathogenesis in mice. Arthritis Rheumatol 66:1504-16
Boespflug, Nicholas D; Kumar, Sachin; McAlees, Jaclyn W et al. (2014) ATF3 is a novel regulator of mouse neutrophil migration. Blood 123:2084-93
Moreno-Fernandez, Maria E; Joedicke, Jara J; Chougnet, Claire A (2014) Regulatory T Cells Diminish HIV Infection in Dendritic Cells - Conventional CD4(+) T Cell Clusters. Front Immunol 5:199
Donnelly, Jessica M; Engevik, Amy; Feng, Rui et al. (2014) Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach. Am J Physiol Gastrointest Liver Physiol 306:G1075-88
Cole, Heather A; Ohba, Tetsuro; Nyman, Jeffry S et al. (2014) Fibrin accumulation secondary to loss of plasmin-mediated fibrinolysis drives inflammatory osteoporosis in mice. Arthritis Rheumatol 66:2222-33
Huang, Wenting; Kachapati, Kritika; Adams, David et al. (2014) Murine autoimmune cholangitis requires two hits: cytotoxic KLRG1(+) CD8 effector cells and defective T regulatory cells. J Autoimmun 50:123-34
Patel, Zubin H; Kottyan, Leah C; Lazaro, Sara et al. (2014) The struggle to find reliable results in exome sequencing data: filtering out Mendelian errors. Front Genet 5:16
Ardoin, Stacy P; Schanberg, Laura Eve; Sandborg, Christy I et al. (2014) Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein. Ann Rheum Dis 73:557-66
Suzuki, Takuji; Mayhew, Christopher; Sallese, Anthony et al. (2014) Use of induced pluripotent stem cells to recapitulate pulmonary alveolar proteinosis pathogenesis. Am J Respir Crit Care Med 189:183-93
Donnelly, Jessica M; Engevik, Amy C; Engevik, Melinda et al. (2014) Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell. Dig Dis Sci 59:569-82

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