Moon G. Kim, Ph.D.
Lead Investigator
Staff Scientist
Thymic Molecular Development Unit
Description of Research Program
In order to understand the development and functioning of the thymus, both in terms of T-cell differentiation and stromal cell environmental support, we have undertaken a molecular approach to identify genes that are uniquely expressed in this organ. We have created an RT-PCR-based subtracted cDNA library from fetal thymic stromal cells and a representative cDNA library from SCID thymus. Four genes were selected for further analysis because they are limited in their expression to the thymus or to one of several thymic stromal cell lines. The three novel genes were named Epithin, Spatial, and Thymic Stromal Co-Transporter (TSCOT).
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A. Green thymus from 3.1Kb-EGFP newborn transgenic mouse
B. Thymic epithelial cells are green, CD45 positive thymocytes are red in Tg mouse
C. The cortical expression of b-gal protein in the newborn TSCOT delta/delta thymus
D. H and E staining of image C |
We are currently attempting to understand the function of two genes (TSCOT and Epithin) in thymocytes and stromal cell development by gene targeting and fetal thymic organ cultures and molecular and biochemical assays. There are two mouse model systems that are currently available to us. One is a transgenic mouse harboring 3.1Kb of the TSCOT promoter driving enhanced green fluorescence protein. This transgene is expressed in the subcapsular and medullary regions of the thymus. The other model is the TSCOT delta mouse, which is expressing the beta galactosidase protein in the cortex. Using these, we are attempting to discern the origin and function of different subcompartments of the thymic stromal environment.
For the next phase of this project, we are generating more mouse models using available molecular reagents, such as thymic stromal compartment-specific cell ablation and conditional knock-in mice with a reporter gene expressed in the targeted locus. These animal models will allow us to study specific thymic stromal cell function in whole animals and organ culture.
Research Group Members (2002)
Gwanghee Lee, Chansik Park, Jason Drury, Eun-Gyung Cho, Heonsik Choi.
Selected Publications
To view a complete listing, visit PubMed.
Kim MG, Chen C, Flomerfelt FA, Germain RN, Schwartz RH. A subtractive PCR-based cDNA library made from fetal thymic stromal cells. J Immunological Methods. 1998. 213:169-182.
Kim MG, Chen C, Lyu MS, Cho EG, Park D, Kozak C, Schwartz RH. Cloning, tissue expression, and mapping of a gene from thymic stromal cells encoding a new mouse type II membrane serine protease with LDL receptor modules and two CUB domains. Immunogenetics. 1999. 49: 420-428.
Kim MG, Flomerfelt FA, Lee KN, Chen C, Schwartz RH. A putative 12 transmembrane domain protein from thymic stromal cells. J Immunol. 2000. 164: 3185-3192.
Flomerfelt F, Kim MG, Schwartz RH. Spatial, a gene expressed in thymic stromal cells, depends on three-dimensional thymus organization for its expression. Genes and Immunity. 2000. 1: 391-401.
Kim MG, Lee G, Lee SK, Lolkema M, Yim J, Hong SH, Schwartz RH. Epithelial Cell-Specific Laminin 5 is Required for Survival of Early Thymocytes. J Immunol. 2000. 165(1): 192-201.
Cho E, Kim MG, Kim C, Kim S, Seong IS, Chung CH, Schwartz RH, Park D. Amino-terminal processing is essential for secretion of epithin, a mouse type II membrane serine protease. J Biol Chem. 2001. 276(48): 44581-44589.
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