International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

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POSTER 73 - A MOUSE MODEL OF INFLAMMATORY ARTHRITIS

Abe K
GSF National Research Centre for Environment and Health

Co-Authors: 1) Wagner S, 2) Kalaydijev S, 1) 3) Jakob T, 1) Soewarto D, 1) Fuchs H, 1) Hrabe de Angelis M
Institutions: 1) GSF National Research Centre for Environment and Health, 2) Institute of Medical Microbiology, TU-München 3) Division of Environmental Dermatology and Allergy, TU-München

Rheumatoid arthritis (RA) is a multifactorial disease involving inflammatory conditions that lead to joint destruction. Despite tremendous efforts in the field, the etiology and molecular pathogenesis of RA remain largely unknown. Therefore, animal models of arthritis provide important tools for the dissection of the molecular mechanisms leading to RA. The dominant mutation, Abnormal limb 18 (Ali18), was isolated from the Munich ENU mutagenesis screen in the mouse. Ali18 homozygous mice display destruction of fingers by severe swelling at adult stages, but have normal lifespan and fertility. Histological examinations revealed that many tissues including joints were destroyed by inflammatory infiltrate that consists of polymorphnuclear leukocytes and lymphocytes. To elucidate how the immune system concerns this phenotype, we analyzed various immunological parameters in peripheral blood of Ali18 mice by ELISA and flow cytometry. Increased B cell populations and elevated levels of antibodies against immunoglobulins were detected in Ali18 homozygous mice, suggesting activation of the immune system. Moreover, proinflammatory cytokines such as IL1β and TNFa , which play important roles in the development of RA, were overexpressed in the joints of these mice. Possible involvement of the Ali18 mutation in rheumatoid arthritis will be discussed. To identify the Ali18 mutation, candidate approach and efforts to narrow down the critical region by genetic mapping are currently underway.