Abstract Myelin oligodendrocyte glycoprotein (MOG)- induced experimental autoimmune encephalomyelitis (EAE) in rats closely mimics the human disease multiple sclerosis (MS). As in MS, genetic predisposition to MOG-EAE is regulated by both MHC and non-MHC genes. Based on disease regulatory influences on MOG- EAE on chromosome 10 in an F2 cross between suscepti- ble DA and resistant ACI rats, we have now isolated this locus in a congenic rat strain to enable further dissection of disease mechanisms. This region is of particular inter- est, since it is homologous to human 17q for which human whole-genome scans have indicated harbors genes regu- lating susceptibility to MS. Phenotypic comparison be- tween DA and the congenic DA.ACI-D10Rat2-D10Rat29 strain confirms that the chromosomal segment harbors gene(s) conferring strong protection against MOG-EAE. Furthermore, resistance to EAE in this congenic strain is associated with absence or a low level of inflammation and demyelination in the central nervous system. Levels of anti-MOG antibody isotypes did not differ between pa- rental and congenic rats, thus an action on Th1/Th2 differ- entiation is unlikely. In conclusion, this is the first exam- ple of an EAE-regulating locus isolated in a congenic rat strain with retained phenotype. The mechanism by which gene(s) in the region act is still unclear and will require further studies with this congenic rat strain as a tool. Keywords Multiple sclerosis · Quantitative trait locus · Congenic strain · Inbred DA rat · Demyelination Introduction Multiple sclerosis (MS) is an inflammatory, demyelinat- ing disease of the central nervous system (CNS) of puta- tive autoimmune etiology. The disease is one of the most common causes of disability among young and middle- aged individuals (Ebers and Sadovnick 1998). Current treatments are only modestly beneficial. The steady in- crease in knowledge of the immunopathogenesis in MS suggests that a variety of different mechanisms can lead to inflammation and demyelination (Lucchinetti et al. 2000), although the cause of the disease remains un- known. There is a polygenic predisposition to MS, but besides the association with HLA class II genes and CD45 (Jacobsen et al. 2000; reviewed by Olerup and Hillert 1991; Tienari et al. 1993), whole-genome scans and association studies have failed to demonstrate con- clusive evidence of linkage or association of a particular locus with MS (reviewed by Dyment et al. 1997; Ebers and Sadovnick 1994). The difficulties in studying both disease mechanisms and genetics in MS motivate studies of animal models, primarily experimental autoimmune encephalomyelitis (EAE) that can be induced in inbred rodents by immunization with myelin antigens in adju- vant. We have previously shown that immunization of ge- netically susceptible inbred rats with myelin oligoden- drocyte glycoprotein (MOG), a minor component of the outer layer of the myelin sheath, induces a disease that mimics MS better than any other EAE model to date (Storch et al. 1998; Weissert et al. 1998). MOG-induced EAE in rats is characterized by a relapsing/remitting dis- ease course as well as focal lesions in the CNS with ex- tensive demyelination and a distribution similar to that in MS (Storch et al. 1998). MOG is unique among CNS au- toantigens, in that it can elicit both a pathogenic T- and a demyelinating B-cell response (Adelmann et al. 1995; M. Jagodic ( ✉ ) · T. Olsson · I. Dahlman Neuroimmunology Unit, Center for Molecular Medicine, L8:04, Karolinska Hospital, 17176 Stockholm, Sweden e-mail: maja.jagodic@cmm.ki.se Tel.: +46-8-51776246, Fax: +46-8-51776248 B. Kornek Department of Neuropsychiatry of Childhood and Adolescence, Währinger Gürtel 18–20, University of Vienna, 1090 Vienna, Austria R. Weissert Department of Neurology, University of Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany H. Lassmann Brain Research Institute, University of Vienna, Spitalgasse 4, 1090 Vienna, Austria Immunogenetics (2001) 53:410–415 DOI 10.1007/s002510100342 ORIGINAL PAPER Maja Jagodic · Barbara Kornek · Robert Weissert Hans Lassmann · Tomas Olsson · Ingrid Dahlman Congenic mapping confirms a locus on rat chromosome 10 conferring strong protection against myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis Received: 19 February 2001 / Revised: 21 May 2001 / Published online: 30 June 2001 © Springer-Verlag 2001