The Genetic Animal Models core will be co-directed by Hans-Christian Reinecker and Cornelis Terhorst. Services offered by the Genetic Animals Models Core include (1) breeding and maintenance of mutant mouse stocks, (2) characterization of murine models, (3) cell isolation from and characterization of murine models of IBD; (4) cell type-specific gene targeting and depletion; (5) bone marrow transfers and adoptive T cell transfers; (6) maintenance of GFP- and RFP-based reporter mice; (7) in vivo tracking of fluorescent cells and labeled bacteria; (8) mouse brightfield and fluorescent endoscopy, (9) whole-body imaging of bioluminescent and fluorescent signals, (10) intravital imaging of immune cells using multiphoton intravital microscopy, and (12) new murine model development. Within the 163 genetic associations currently known to be associated with risk of IBD, an increasing number of rare variants have highlighted the significance of the relationship between intracellular responses to microbes and regulation of adaptive immunity in the pathogenesis of IBD. However, the in vivo functional context in which these genetic variations affect epithelial intestinal function and immune responses remains to be elucidated. To address this need, the Core will assist investigators in using or developing model systems to examine the cell-specific function of variants, and will provide support for examining the functional role of these variants and their contribution to barrier function and innate and adaptive immunity.
The specific aims of the Genetic Animal Models Core are to (1) support investigations in mice aimed at elucidating the contribution of IBD-related genetic variants and related genes to the pathogenesis of IBD in humans; (2) facilitate functional in vitro and in vivo imaging of cellular responses and migration in the mucosal and peripheral immune system; and (3) support sharing of model systems and tools to foster collaborations among CSIBD investigators.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK043351-28
Application #
9399650
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
28
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
Qu, Chen; Zheng, Dandan; Li, Sai et al. (2018) Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis. Hepatology :
Simon, Tracey G; King, Lindsay Y; Chong, Dawn Q et al. (2018) Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology 67:1797-1806
Borren, Nienke Z; Conway, Grace; Garber, John J et al. (2018) Differences in Clinical Course, Genetics, and the Microbiome Between Familial and Sporadic Inflammatory Bowel Diseases. J Crohns Colitis 12:525-531
Battistone, Maria A; Nair, Anil V; Barton, Claire R et al. (2018) Extracellular Adenosine Stimulates Vacuolar ATPase-Dependent Proton Secretion in Medullary Intercalated Cells. J Am Soc Nephrol 29:545-556
Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan et al. (2018) Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 67:108-119
Chandradas, Sajiv; Khalili, Hamed; Ananthakrishnan, Ashwin et al. (2018) Does Obesity Influence the Risk of Clostridium difficile Infection Among Patients with Ulcerative Colitis? Dig Dis Sci 63:2445-2450
Luther, Jay; Gala, Manish; Patel, Suraj J et al. (2018) Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn's Disease Is Not Associated with Emergence of Novel Inflammatory Pathways. Dig Dis Sci 63:738-745
Graham, Daniel B; Luo, Chengwei; O'Connell, Daniel J et al. (2018) Antigen discovery and specification of immunodominance hierarchies for MHCII-restricted epitopes. Nat Med 24:1762-1772
Schirmer, Melanie; Franzosa, Eric A; Lloyd-Price, Jason et al. (2018) Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol 3:337-346
Cheung, Pui W; Terlouw, Abby; Janssen, Sam Antoon et al. (2018) Inhibition of non-receptor tyrosine kinase Src induces phosphoserine 256-independent aquaporin-2 membrane accumulation. J Physiol :

Showing the most recent 10 out of 1166 publications