David L. Gasser, Ph.D.

faculty photo
Emeritus Professor of Genetics
Department: Genetics

Contact information
575 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6145
Office: 215-898-5175
Fax: 215-573-5892
B.S. (Biology)
University of Akron, 1964.
M.S. (Zoology)
University of Michigan, 1966.
Ph.D. (Zoology)
University of Michigan, 1970.
Permanent link
> Perelman School of Medicine   > Faculty   > Details

Description of Research Expertise

Research Interests

Mouse models of human disease

Key words: kidney, autoimmune disease, mitochondria

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. We have cloned the relevant gene, and have found that it codes for a mitochondrial protein similar to trans-prenyltransferase. This enzyme is needed for isoprenylation of coenzyme Q (CoQ), and is now known as prenyl diphosphate synthase subunit 2 (Pdss2). The mutant mice have defective mitochondria, as demonstrated by ultrastructural analysis, and we believe that this defect leads to the death of glomerular podocytes. This in turn leads to an autoimmune response which involves both the tubular interstitium and the glomeruli. The kidney disease can be prevented to some extent by CoQ supplementation, and to an even greater extent by probucol.

In collaboration with Dr. Julie Blendy, Dr. Harry Ischiropoulos, and their students, we have demonstrated that these mutant mice also have neuromuscular defects that resemble Parkinson’s disease.

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 in collaboration with a group at the NIH, we have obtained evidence that PDSS2 is one of the genes that is involved in this susceptibility.

Lab Personnel:

Min Peng, MD,PhD, Research Specialist

Selected Publications

Gasser, D. L., Winkler, C. A., Peng, M., An, P., McKenzie, L. M., Kirk, G. D., Shi, Y., Xie, L. X., Marbois, B. N., Clarke, C. F., Kopp, J. B.: Focal segmental glomerulosclerosis is associated with a PDSS2 haplotype and, independently, with a decreased content of coenzyme Q10. American journal of physiology. Renal physiology 305(8): F1228-38, 2013.

Ziegler, Carly G. K., Peng, Min, Falk, Marni J., Polyak, Erzsebet, Tsika, Elpida, Ischiropoulos, Harry, Bakalar, Dana, Blendy, Julie A., Gasser, David L.: Parkinson''s disease-like neuromuscular defects occur in prenyl diphosphate synthase subunit 2 (Pdss2) mutant mice. Mitochondrion 12(2): 248-257, 2012.

Falk, M. J., Polyak, E., Zhang, Z., Peng, M., King, R., Maltzman, J. S., Okwuego, E., Horyn, O., Nakamaru-Ogiso, E., Ostrovsky, J., Xie, L. X., Chen, J. Y., Marbois, B., Nissim, I., Clarke, C. F., Gasser, D. L.: Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice. EMBO Mol Med 3(7): 410-27, 2011.

Peng, M., Falk, M. J., Haase, V. H., King, R., Polyak, E., Selak, M., Yudkoff, M., Hancock, W. W., Meade, R., Saiki, R., Lunceford, A. L., Clarke, C. F., and Gasser, D, L.: Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease. PLoS Genetics 4(4): e1000061, 2008.

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.

back to top
Last updated: 10/22/2013
The Trustees of the University of Pennsylvania