c
2
12
18
28
12
12
1a
14
e
12
16
a
a
2
2
a
20
32
1a
2a
19
Faculty
61 16
19
1
49
2
2
1a
32
34
1b
1d
18
34
43
1d
2 29
1d
25
David L. Gasser, Ph.D.
78
43
Emeritus Professor of Genetics
7
5f
Department: Genetics
4
1
b
1d
46
Contact information
4c
4
3
3
1d
4c
575 Clinical Research Building
3b 415 Curie Boulevard
Philadelphia, PA 19104-6145
26
3b 415 Curie Boulevard
Philadelphia, PA 19104-6145
2e
Office: 215-898-5175
32 Fax: 215-573-5892
24
95
32 Fax: 215-573-5892
24
Email:
GASSERD@MAIL.MED.UPENN.EDU
12
GASSERD@MAIL.MED.UPENN.EDU
18
Publications
23 a
3
2
4
b
1f
23 a
13
Education:
21 9 B.S. 14 (Biology) c
2c University of Akron, 1964.
21 9 M.S. 14 (Zoology) c
2f University of Michigan, 1966.
21 a Ph.D. 14 (Zoology) c
2f University of Michigan, 1970.
c
3
27
21 9 B.S. 14 (Biology) c
2c University of Akron, 1964.
21 9 M.S. 14 (Zoology) c
2f University of Michigan, 1966.
21 a Ph.D. 14 (Zoology) c
2f University of Michigan, 1970.
c
Links
99 Search PubMed for articles
46 Cell and Molecular Biology graduate group faculty webpage.
42 Immunology graduate group faculty webpage.
c
5
3
3
90
Permanent link99 Search PubMed for articles
46 Cell and Molecular Biology graduate group faculty webpage.
42 Immunology graduate group faculty webpage.
c
2 29
21
1e
1d
24
5e
8
25 Mouse models of human disease
8
42 Key words: kidney, autoimmune disease, mitochondria
8
26 Description of Research
8
34d 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.
8
cd 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.
8
161 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.
8
1e Lab Personnel:
8
2c Min Peng, MD,PhD, Research Specialist
26 29
27
Description of Research Expertise
2b Research Interests8
25 Mouse models of human disease
8
42 Key words: kidney, autoimmune disease, mitochondria
8
26 Description of Research
8
34d 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.
8
cd 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.
8
161 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.
8
1e Lab Personnel:
8
2c Min Peng, MD,PhD, Research Specialist
26 29
23
183 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.
1ae 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.
16b 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.
11b 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.
145 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.
130 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.
dc 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.
10c 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.
2c
7
1d
1f
Selected Publications
1b1 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, 2013.183 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.
1ae 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.
16b 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.
11b 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.
145 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.
130 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.
dc 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.
10c 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.
2c
4d
22
22
7
10
a
a
2
2
19
18
10
22
10
11
c
5b © The Trustees of the University of Pennsylvania | Site best viewed a in a supported browser. | Site Design: 57 PMACS Web Team. 3 22
10