Research Interests
Genes that affect the immune response
Key words: kidney, autoimmune disease.
Description of Research
We are studying a mutant gene which when homozygous leads to a lethal kidney disease in mice. These mice undergo a spontaneous autoimmune reaction which involves multiple immune pathways. Effector T cells are involved, as well as natural killer (NK) cells. We have reason to believe that regulatory NKT cells also participate.
We have cloned the relevant gene, and have found that it codes for a mitochondrial protein similar to trans-prenyltransferase. In other organisms, this enzyme is needed for isoprenylation of coenzyme Q. The mutant mice have defective mitochondria, as demonstrated by ultrastructural analysis, and we believe that this defect leads to apoptosis in both renal tubular epithelial cells and glomerular podocytes. This in turn leads to an autoimmune response which involves both the tubular interstitium and the glomeruli.
The human disease with the greatest similarity to this phenotype is focal segmental glomerular sclerosis, or FSGS. It is well known that there is a significant genetic component to FSGS susceptibility, and we are exploring the possibility that the human counterpart of this prenyltransferase-like mitochondrial protein (PLMP) is one of the genes that is involved in this susceptibility.
Rotation Projects for 2006-2007
Investigation of NK effector cells and NKT regulatory cells by immunohistochemistry, fluorescence-activated cell sorting, and genetic crosses with strains that are deficient in those functions.
Lab personnel:
Min Peng, MD,PhD, Research Specialist
Zhaohui Wang, M.D. Visiting Scientist
Selected Publications
Hallman, T.M., Peng, M., Meade, R., Hancock, W.W., Madaio, M.P. and Gasser, D.L.: The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions. Journal of Autoimmunity 26: 1-6, 2006.
Madaio, M. P., Ahima, R.S., Meade, R., Rader D.J., Mendoza, A., Peng, M., Tomaszewski, J. E., Hancock, W. W. and Gasser, D. L.: Glomerular and tubular epithelial defects in kd/kd mice lead to progressive renal failure. Am. J. Nephrol 25: 604-610, 2005.
Peng M, Jarett L, Meade R, Madaio MP, Hancock WW, George AL, Neilson EG and Gasser DL: Mutant prenyltransferase-like mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice. Kidney International 66: 20-28, 2004.
Hancock WW, T-L Tsai, MP Madaio, and DL Gasser: Cutting edge: Multiple autoimmune pathways in kdkd mice. Journal of Immunology 171: 2778-81, 2003.
Dell, K.M., Li, Y.X., Peng, M., Nielson, E.G., and Gasser, D.L.: Localization of the mouse kidney disease (kd) gene to a YAC/BAC contig on mouse chromosome 10. Mammalian Genome 11: 967-971, 2000.
Bedian V., Adams T., Geiger EA., Bailey LC., Gasser DL.: A gene belonging to the Sm family of snRNP core proteins maps within the mouse MHC. Immunogenetics 46(5): 427-30, 1997.
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Last updated: 07/10/2008
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