Abstract

The long-term objectives of this research program are to use newly found immunological mutants of the mouse to investigate the etiology of immunodeficiency and autoimmune diseases and to ascertain the role of the immune system in the development of spontaneous neoplasms. The main objectives of the current project are to determine the underlying cellular and biochemical basis for development and immunological defects, polyclonal B-cell activation, and pathologic abnormalities in motheaten (me/me) and viable motheaten (me?v?/me?v?) mice. Homozygosity for these deleterious alleles at the motheaten locus causes the most severe, genetically determined immunologic dysregulation known in mice.
The specific aims i nclude: (1) evaluation of the effects of depleting B cells or T cells in vivo on immunopathologic states; (2) determination of the roles of soluble lymphokines in the induction of B-cell differentiation in normal resting B cells and in B cell tumor lines; (3) analysis of parameters of macrophage activation; (4) evaluation of the role of Ia antigen expression on inappropriate cellular interactions; and (5) assessment of the mechanism of pulmonary injury in irradiated recipients of bone marrow cells from me/me mice. These studies will contribute to an understanding of complex immunologic diseases of genetic origin and increase our knowledge about the immune system in normal and pathologic states. (SR)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA020408-10
Application #
3165271
Study Section
Immunobiology Study Section (IMB)
Project Start
1976-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

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

  Publications

Saito, Yoriko; Uchida, Naoyuki; Tanaka, Satoshi et al. (2010) Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Nat Biotechnol 28:275-80
Yamamoto, Takashi; Kaizu, Chikako; Kawasaki, Takashi et al. (2008) Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (op/op) mice after macrophage depletion. Cell Tissue Res 332:245-56
Chen, Jian; Wu, Qi; Yang, Pingar et al. (2006) Determination of specific CD4 and CD8 T cell epitopes after AAV2- and AAV8-hF.IX gene therapy. Mol Ther 13:260-9
Huang, Zan; Coleman, John M; Su, Yan et al. (2005) SHP-1 regulates STAT6 phosphorylation and IL-4-mediated function in a cell type-specific manner. Cytokine 29:118-24
Zhang, Huang-Ge; High, Katherine A; Wu, Qi et al. (2005) Genetic analysis of the antibody response to AAV2 and factor IX. Mol Ther 11:866-74
Park, Il-Kyoo; Shultz, Leonard D; Letterio, John J et al. (2005) TGF-beta1 inhibits T-bet induction by IFN-gamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1. J Immunol 175:5666-74
Li, Lina; Hsu, Hui-Chen; Stockard, Cecil R et al. (2004) IL-12 inhibits thymic involution by enhancing IL-7- and IL-2-induced thymocyte proliferation. J Immunol 172:2909-16
Hayashi, Shin-Ichi; Tsuneto, Motokazu; Yamada, Takayuki et al. (2004) Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice. Endocrinology 145:2721-9
Zhang, H-G; Hsu, H-C; Yang, P-A et al. (2004) Identification of multiple genetic loci that regulate adenovirus gene therapy. Gene Ther 11:4-14
Makatsori, Dimitra; Kourmouli, Niki; Polioudaki, Hara et al. (2004) The inner nuclear membrane protein lamin B receptor forms distinct microdomains and links epigenetically marked chromatin to the nuclear envelope. J Biol Chem 279:25567-73

Showing the most recent 10 out of 129 publications