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
02114
Molinie, Benoit; Giallourakis, Cosmas C (2017) Genome-Wide Location Analyses of N6-Methyladenosine Modifications (m6A-Seq). Methods Mol Biol 1562:45-53
Schwerd, Tobias; Pandey, Sumeet; Yang, Huei-Ting et al. (2017) Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease. Gut 66:1060-1073
Gevers, Dirk; Kugathasan, Subra; Knights, Dan et al. (2017) A Microbiome Foundation for the Study of Crohn's Disease. Cell Host Microbe 21:301-304
Jung, Keehoon; Heishi, Takahiro; Khan, Omar F et al. (2017) Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy. J Clin Invest 127:3039-3051
Rooks, Michelle G; Veiga, Patrick; Reeves, Analise Z et al. (2017) QseC inhibition as an antivirulence approach for colitis-associated bacteria. Proc Natl Acad Sci U S A 114:142-147
Maehara, Takashi; Mattoo, Hamid; Ohta, Miho et al. (2017) Lesional CD4+ IFN-?+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. Ann Rheum Dis 76:377-385
Ananthakrishnan, Ashwin N; Luo, Chengwei; Yajnik, Vijay et al. (2017) Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases. Cell Host Microbe 21:603-610.e3
Canali, Susanna; Zumbrennen-Bullough, Kimberly B; Core, Amanda B et al. (2017) Endothelial cells produce bone morphogenetic protein 6 required for iron homeostasis in mice. Blood 129:405-414
Ananthakrishnan, A N; Sakuraba, A; Barnes, E L et al. (2017) The benefit of combination therapy depends on disease phenotype and duration in Crohn's disease. Aliment Pharmacol Ther 46:162-168
Miyabe, Chie; Miyabe, Yoshishige; Strle, Klemen et al. (2017) An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL-6 blockade therapy. Ann Rheum Dis 76:898-905

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