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.
 
Left: ANA antibody from a scleroderma mouse model, Right: Skin from a scleroderma mouse model and control
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.
Mapping a diabetes gene in rats and human cohorts: Ubd is a candidate gene
Selected publications: (See all Elizabeth Blankenhorn's publications in PubMed.)
The postnatal maternal environment affects autoimmune disease susceptibility in A/J mice.
Case LK, Del Rio R, Bonney EA, Zachary JF, Blankenhorn EP, Tung KS, and C Teuscher.
Immunology & Cell Biology 260(2): 119-127, 2010.
Infection with viruses from several families triggers autoimmune diabetes in LEW.1WR1 rats: prevention of diabetes by maternal immunization.
Tirabassi RS, Guberski DL, Blankenhorn EP, Leif JH, Woda BA, Liu Z, Winans D, Greiner DL, and JP Mordes
Diabetes, 59(1): 110-118, 2009.
A single nucleotide polymorphism in Tyk2 controls susceptibility to experimental allergic encephalomyelitis.
Spach KM, Noubade R, McElvany B, Hickey WF, Blankenhorn EP, and C Teuscher.
The Journal of Immunology, 182(12): 7776-7783, 2009.
Cutting edge: the Y chromosome controls the age-dependent experimental allergic encephalomyelitis sexual dimorphism in SJL/J mice.
Spach KM, Blake M, Bunn JY, McElvany B, Noubade R, Blankenhorn EP, an C Teuscher.
The Journal of Immunology, 182: 1789-1793, 2009.
Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus.
Mordes JP, Cort L, Norowski E, Leif J, Fuller JM, Lernmark A, Greiner DL, and EP Blankenhorn.
Mammalian Genome, 2009 (3): 162-169, 2009.
Genetic dissection reveals diabetes loci proximal to the gimap5 lymphopenia gene.
Fuller JM, Bogdani M, Tupling T D, Jensen RA, Pefley R, Manavi S, Cort L, Blankenhorn EP, Mordes JP, Lernmark A, and AE Kwitek
Physiological Genomics, 10;38(1): 89-97, 2009.
Virus-induced autoimmune diabetes in the LEW.1WR1 rat requires Iddm14 and a locus proximal to the major histocompatibility complex.
Blankenhorn EP, Cort L, Greiner DL, Guberski DL, and JP Mordes.
Diabetes, 58: 2930-2938, 2009.
Genetic loci that regulate healing and regeneration in LG/J and SM/J mice.
Blankenhorn EP, Bryan G, Kossenkov AV, Clark LD, Zhang XM, Chang C, Horng W, Pletscher LS, Cheverud JM, Showe LC, and E Heber-Katz
Mamm.
Genome, 20: 720-733. 2009.
Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS.
Teuscher C, Subramanian M, Noubade R, Gao JF, Offner H, Zachary JF, and EP Blankenhorn.
Proceedings of the National Academy of Sciences of the United States of America, 104(24): 10146-10151, 2007.
Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-gamma production in mice.
Noubade R, Milligan G, Zachary JF, Blankenhorn EP, del Rio R, Rincon M, and C Teuscher.
Journal of Clinical Investigation 117(11): 3507-3518, 2007.
Evidence that the Y-Chromosome influences EAE in male and female mice.
Teuscher C, Noubade R, Spach K, Bunn JY, Fillmore PD, Zachary JF, and EP Blankenhorn
Proceedings of the National Academy of Sciences. 103: 8024-8029, 2006.
Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. castaneus mice.
Heber-Katz E, Chen P, Clark L, Zhang X, Troutman S, and EP Blankenhorn.
Wound Repair and Regeneration - Journal Information., 12:384-392, 2004.
et al. Complex Trait Consortium. The nature and identification of quantitative trait loci: a community's view.
Abiola O, Angel JM, Avner P, Bachmanov AA, Belknap JK, Bennett B, Blankenhorn EP
Nature Reviews Genetics, 4: 911-916, 2003.
Mapping of genes involved in murine herpes simplex virus keratitis: Identification of genes and their modifiers.
Norose K, Yano A, Zhang XM, Blankenhorn EP, and E Heber-Katz.
The Journal of Virology, 76: 3502-3510, 2002.
Identification of Bphs, an Autoimmune Disease Locus, as Histamine Receptor H1.
Ma RZ, Gao J, Meeker ND, Fillmore PD, Tung KSK, WatanabeT, Zachary JF, Offner H, Blankenhorn EP, and C Teuscher.
Science, 297: 620-623, 2002
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