The mouse colony, genotyping and antibody core (MCGAC) will I. Breed and genotype the genetically engineered mice generated for and during the program project period. The core will generate crosses and backcrosses to obtain mice in the desired genetic background. II. Generate monoclonal antibodies to NWASP, WASP and to any other proteins requested by the investigators. The cost of animal housing is becoming very expensive;therefore it is impossible for individual investigator to maintain colonies of all the genetically engineered mice necessary for the program project. MCGAC will centralize the maintenance of breeder colony and coordinate breeding of experimental animals in parallel for more than one investigator. Working as a group should result in minimal animal wastage and cost savings. Because of the location of Dr. Snapper's laboratory at MGH, he will maintain his own mouse colony. This is reflected in the budgets of Project #2, which includes mouse costs. Nevertheless, every effort will be made to save costs by sharing tissues among all 4 investigators whenever possible.
The second aim of the MCGAC is to generate, characterize and standardize the mAbs against the proteins being investigated in the program project. Many of the proteins investigated in the program project are novel and the investigators have to depend on the few commercial antibodies or antisera that are available against these proteins. Purchase of antibodies adds a significant expense to the Program project investigators. MCGAC will generate virtually inexhaustible supply of several monoclonal antibodies that will not only benefit the investigators of the Program Project but also the WASP research community at large.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL059561-13
Application #
8148007
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2010-09-01
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
13
Fiscal Year
2010
Total Cost
$304,358
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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Vardi, Iddo; Barel, Ortal; Sperber, Michal et al. (2018) Genetic and Structural Analysis of a SKIV2L Mutation Causing Tricho-hepato-enteric Syndrome. Dig Dis Sci 63:1192-1199
Li, Jian; Shouval, Dror S; Doty, Andria L et al. (2017) Increased Mucosal IL-22 Production of an IL-10RA Mutation Patient Following Anakin Treatment Suggests Further Mechanism for Mucosal Healing. J Clin Immunol 37:104-107
Lexmond, Willem S; Goettel, Jeremy A; Lyons, Jonathan J et al. (2016) FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy. J Clin Invest 126:4030-4044
Baptista, Marisa A P; Keszei, Marton; Oliveira, Mariana et al. (2016) Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells. Nat Commun 7:12175
Volpi, Stefano; Santori, Elettra; Abernethy, Katrina et al. (2016) N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome. Blood 127:216-20
Moran, Christopher J; Klein, Christoph; Muise, Aleixo M et al. (2015) Very early-onset inflammatory bowel disease: gaining insight through focused discovery. Inflamm Bowel Dis 21:1166-75
Crestani, Elena; Volpi, Stefano; Candotti, Fabio et al. (2015) Broad spectrum of autoantibodies in patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia. J Allergy Clin Immunol 136:1401-4.e1-3
Kolhatkar, Nikita S; Brahmandam, Archana; Thouvenel, Christopher D et al. (2015) Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome. J Exp Med 212:1663-77
Gerasimcik, Natalija; Dahlberg, Carin I M; Baptista, Marisa A P et al. (2015) The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B Cells. J Immunol 194:4750-8

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