Abstract

Although chromosomal locations for a number of non-MHC genes have been established in mice, their actual identities and precise functions remain unknown. Resistance alleles at two loci on chromosome 3, IDD3 and IDD10, together confer strong diabetes protection in NOD. Congenic mice have defects in the development and maturation of marrow-derived antigen presenting cells (APC), including macrophages, sufficiently severe to impair IL-1 secretory responses. These defects are reversed in the IDD3-IDD10 congenic stock, leading to the hypothesis that products of these alleles, in the presence of the NOD H2, collectively contribute to reduced ability of APC to activate immunoregulatory pathways. This project has three aims. The first is to determine which specific macrophage developmental anomalies in NOD mice are individually or synergistically controlled by IDD3 or IDD10, using existing congenic stocks.
The second aim will use differential display analysis to detect genes that are differentially expressed.
The third aim will use bone marrow chimeras and fetal thymic organ culture to study the function of the impaired APC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036175-13
Application #
2734041
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Akolkar, Beena
Project Start
1985-07-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609

  Publications

Chen, Jing; Gusdon, Aaron M; Piganelli, Jon et al. (2011) mt-Nd2(a) Modifies resistance against autoimmune type 1 diabetes in NOD mice at the level of the pancreatic ?-cell. Diabetes 60:355-9
Chen, Yi-Guang; Scheuplein, Felix; Driver, John P et al. (2011) Testing the role of P2X7 receptors in the development of type 1 diabetes in nonobese diabetic mice. J Immunol 186:4278-84
Chen, Jing; Lu, Ying; Lee, Chul-Ho et al. (2008) Commonalities of genetic resistance to spontaneous autoimmune and free radical--mediated diabetes. Free Radic Biol Med 45:1263-70
Reifsnyder, Peter; Schott, William; Pomerleau, Darcy et al. (2008) Bone marrow expressing a diabetes resistance MHC class II allele: diabetes deviation by chronic immune stimulation. Novartis Found Symp 292:32-46;discussion 46-9, 122-9, 2
Leiter, E H; Reifsnyder, P; Driver, J et al. (2007) Unexpected functional consequences of xenogeneic transgene expression in beta-cells of NOD mice. Diabetes Obes Metab 9 Suppl 2:14-22
Chen, Jing; Chen, Yi-Guang; Reifsnyder, Peter C et al. (2006) Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion. J Immunol 176:4590-9
Lee, Chul-Ho; Chen, Yi-Guang; Chen, Jing et al. (2006) Novel leptin receptor mutation in NOD/LtJ mice suppresses type 1 diabetes progression: II. Immunologic analysis. Diabetes 55:171-8
Chen, Yi-Guang; Chen, Jing; Osborne, Melissa A et al. (2006) CD38 is required for the peripheral survival of immunotolerogenic CD4+ invariant NK T cells in nonobese diabetic mice. J Immunol 177:2939-47
Krebs, Christian; Adriouch, Sahil; Braasch, Fenja et al. (2005) CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins. J Immunol 174:3298-305
Chen, Jing; Reifsnyder, Peter C; Scheuplein, Felix et al. (2005) ""Agouti NOD"": identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells. Mamm Genome 16:775-83

Showing the most recent 10 out of 85 publications