International Immunology, Vol. 13, No. 3, 257-264,
March 2001
© 2001 Japanese Society for Immunology
Identification of genetic loci associated with paralysis, inflammation and weight loss in mouse experimental autoimmune encephalomyelitis
1 Center for Neurologic Diseases, Department of Medicine, Brigham & Women's Hospital and
2 Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
3 E. K. Shriver Center, Waltham, MA 02254, USA
4 Department of Pathology, Stanford University School of Medicine and Laboratory Service, Veterans Health Care System, Palo Alto, CA 94304, USA
5 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Correspondence to: V. K. Kuchroo
Experimental autoimmune encephalomyelits (EAE), a model for human multiple sclerosis, is an inducible inflammatory and demyelinating disease of the central nervous system (CNS). Susceptibility to this disease is heritable and is demonstrated by the development of an ascending paralysis accompanied by a loss in body wt 2–3 weeks following immunization with proteins derived from CNS myelin. In a previous genetic analysis of susceptibility to EAE in a cross between susceptible SJL/J mice and resistant B10.S mice, we found suggestive evidence of linkage with disease susceptibility at the telomeric end of chromosome 2 and in the central region of chromosome 3. To define these associations more precisely and to investigate the genetic factors controlling measurable phenotypes of EAE, we performed a new analysis with a larger number of mice. The results now indicate that the chromosome 2 locus significantly influences EAE-related weight loss (P = 6.7 x 10–5) and that the chromosome 3 locus is linked with the development of paralysis. In addition, an intriguing inheritance pattern was revealed in which female backcross mice generated from B10.S female x (B10.S x SJL/J)F1 male parents experienced significantly more EAE-related weight loss (P = 1.2 x 10–4) than females generated from F1 female x B10.S male parents. After controlling for this inheritance, a new locus at the centromeric end of chromosome 8 was identified that significantly influences both the development of paralysis (P = 8.2 x 10–6) and the incidence of CNS inflammation (P = 7.0 x 10–5) in EAE.
Keywords: C57BL, chromosome mapping, disease susceptibility, genetic crosses, genetic markers, human, inbred strains, incidence, linkage, multiple sclerosis, SJL, quantitative trait
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