The long term objectives of this research program are to utilize newly found immunological mutants of the mouse to investigate the etiology of immunodeficiency and autoimmune diseases. This research proposal focuses on phenotypic abnormalities caused by deleterious alleles at the motheaten locus. Homozygosity for the """"""""motheaten"""""""" (me) and """"""""viable motheaten"""""""" (mev) mutations results in the most severe genetically determined immunologic dysfunction known in experimental animals. It is hypothesized that these mutations cause microenvironmental defects demonstrable at the level of hematopoietic progenitors in the fetal liver and bone marrow. The main objectives of the current program are to assess the roles of hematopoietic progenitor cell abnormalities and microenvironmental defects in the development of immunopathologic changes in me/me and mev/mev mice.
The specific aims i nclude: determination of the cellular basis for defective thymic repopulation following intravenous transfer of bone marrow cells from mev/mev mice into irradiated normal recipients; assessment of dendritic accessory cell abnormalities in me/me and mev/mev mice; determination of the role of hematopoietic progenitor abnormalities in development of immunopathologic changes in these mice; and evaluation of genetic interactions between deleterious alleles at the motheaten locus and the """"""""severe combined immunodeficiency"""""""" (scid) locus. These studies will contribute to an understanding of complex immunologic diseases and increase our understanding of the immune system in normal and pathologic states.
|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