Elizabeth Blankenhorn Professor, Microbiology and Immunology Ph.D., 1979, California Institute of Technology, Pasadena, CA 2900 Queen Lane Philadelphia, PA 19129 Tel :(215) 991-8392 Fax: (215) 848-2271 Email: libby@drexelmed.edu

Research Staff: Laura Cort, Julia Krout, Greg Bryan, Bridget McLaughlin
Graduate Students: Angela Richardson

Keywords:

Immunogenetics, molecular approaches, positional cloning, candidate gene, gene expression, autoimmunity, natural alleles, quantitative inheritance

Research Interests:

The goal of the research in our laboratory is to understand the genetic basis for inherited susceptibility to autoimmune diseases, including diabetes and multiple sclerosis, and the genetic architecture of wound healing. Backcross and F2 progeny are screened for alleles at a large number of genetic loci. The inheritance of these alleles is compared to the inheritance of the phenotype (“linked”) and a preliminary assignment of the location of incidence and quantitative trait loci (QTL) is made. The QTL are confirmed in subsequent crosses, or are fixed in the genome by selective breeding, for the purpose of positional cloning and identification of the disease gene itself.

We currently have several projects underway, including studies to examine the genetic control of susceptibility to experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, in mice. A second project is to map EAE-susceptibility loci in the LEW rat, the prototype strain for this phenotype, and to understand the role of the TCR haplotype in severity of EAE. In recent years, we have applied this method to study susceptibility to retroviral infections and induced lymphomas in mice. We are extending our finding that diabetes in the DP-BB rat is controlled by a QTL we discovered on chromosome 4. This work also involves making a congenic for the chromosome 4 diabetogenic locus to provide material for positional cloning of this QTL. Finally, in collaboration with the Wistar Institute, we are mapping wound healing genes in several large crosses to confirm our original mapping of six QTL associated with the trait of wound healing/regeneration, and to understand the significant sexual dimorphism in the genetic control of this trait.

Selected Publications:

1. Hornum, L., DeScipio, C., Markholst, H., Troutman, S. A., Novak, S., Leif, J., Greiner, D., Mordes, J. P., and E. P. Blankenhorn.  Comparative mapping of rat Iddm4 to segments on HSA7 and MMU6.  Mamm. Genome, 15 (1): 53-61, 2004.
   
   
2. Teuscher, C., Poynter, M. E., Offner, H., Zamora, A., Watanabe, T., Fillmore, P. D., Zachary, J. F., and E. P. Blankenhorn.  Attenuation of Th1 effector cell responses and susceptibility to experimental allergic encephalomyelitis in histamine H2 receptor knockout mice is due to dysregulation of cytokine production by antigen-presenting cells.  Am. J. Pathol., 164: 883-892, 2004.
   
   
3. Polanczyk, M., Yellayi, S., Zamora, A., Subramanian, S., Tovey, M., Vandenbark, A. A., Offner, H., Zachary, J. F., Fillmore, P. D., Blankenhorn, E. P., Gustafsson, J. A., and C. Teuscher.  Estrogen receptor-1 (Esr1) and -2 (Esr2) regulate the severity of clinical experimental allergic encephalomyelitis in male mice.  Am. J. Pathol., 164: 1915-1924, 2004.
   
   
4. Heber-Katz, E., Chen, P., Clark, L., Zhang, X. M., Troutman, S., and E. P. Blankenhorn. Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. Castaneus mice.  Wound Repair Regen., 12: 384-392, 2004.
   
   
5. Mordes, J. P., Bortell, R., Blankenhorn, E. P., Rossini, A. A., and D. L. Greiner.  Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J., 45: 278-291, 2004.
   
   
6. Teuscher, C., Bunn, J. Y., Fillmore, P. D., Butterfield, R. J., Zachary, J. F., and E. P. Blankenhorn.  Gender, age, and season at immunization uniquely influence the genetic control of susceptibility to histopathological lesions and clinical signs of experimental allergic encephalo myelitis: implications for the genetics of multiple sclerosis.  Am. J. Pathol., 165: 1593-1602, 2004.
   
   
7. Alexander, G. M., Erwin, K. L., Byers, N., Deitch, J. S., Augelli, B. J., Blankenhorn, E. P., and T. D. Heiman-Patterson. Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse model of ALS.  Brain Res. Mol. Brain Res., 130: 7-15, 2004.
   
   
8. Heiman-Patterson, T. D., Deitch, J. S., Blankenhorn, E. P., Erwin, K. L., Perreault, M. J., Alexander, B. K., Byers, N., Toman, I., and G. M. Alexander.  Background and gender effects on survival in the TgN(SOD1-G93A)1Gur mouse model of ALS.  J. Neurol. Sci., 236: 1-7, 2005.
   
   
9. Blankenhorn, E. P., Rodemich, L., Martin-Fernandez, C., Leif, J., Greiner, D. L., and J. P. Mordes.  The rat diabetes susceptibility locus Iddm4 and at least one additional gene are required for autoimmune diabetes induced by viral infection.  Diabetes, 54: 1233-1237, 2005.
   
   
10. Teuscher, C., Doerge, R. W., Fillmore, P. D., and E.P. Blankenhorn.  eae36, a locus on mouse chromosome 4, controls susceptibility to experimental allergic encephalomyelitis in older mice and mice immunized in the winter.  Genetics, 172(2): 1147-1153, 2006.
    
    
11. Teuscher, C., Noubade, R., Spach, K., McElvany, B., Bunn, J. Y., Fillmore, P. D., Zachary, J. F., and E. P. Blankenhorn.  Evidence that the Y chromosome influences autoimmune disease in male and female mice.  Proc. Natl. Acad. Sci. U S A, 103(21): 8024-8029, 2006.
    
    
12. Cunningham, T. J., Yao, L., Oetinger, M., Cort, L., Blankenhorn, E. P., and J. I. Greenstein.  Secreted phospholipase A2 activity in experimental autoimmune encephalomyelitis and multiple sclerosis.  J. Neuroinflammation, 3(1): 26, 2006.
    
    
13. Teuscher, C., Subramanian, M., Noubade, R., Gao, J. F., Offner, H., Zachary, J. F., and E. P. Blankenhorn.  Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS.  Proc. Natl. Acad. Sci. U S A, 104(24): 10146-10151, 2007.
    
    
14. Wallis, R. H., Wang, K., Dabrowski, D., Marandi, L., Ning, T., Hsieh, E., Paterson, A. D., Mordes, J. P., Blankenhorn, E. P., and P. Poussier.  A novel susceptibility locus on rat chromosome 8 affects spontaneous but not experimentally induced type 1 diabetes.  Diabetes, 56(6): 1731-1736, 2007.
    
    
15. Blankenhorn, E. P., Descipio, C., Rodemich, L., Cort, L., Leif, J. H., Greiner, D. L., Mordes J. P.  Refinement of the Iddm4 diabetes susceptibility locus reveals TCRVbeta4 as a candidate gene.  Ann. N. Y. Acad. Sci., 1103: 128-131, 2007.