International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

TUESDAY 11 NOVEMBER
10:15 – 10:30 HRS

PHENOTYPIC ANALYSIS AND CHROMOSOMAL MAPPING OF MOUSE MUTANTS WITH CLINICALLY RELEVANT ALTERATIONS OF THE IMMUNE SYSTEM

Flaswinkel H
Institute of Molecular Animal Breeding, Gene Center, Feodor-Lynen-Str. 25 82377 München, Germany

Co-Authors: 1) Rathkolb B, 2) Reindl W, 1) Howaldt M, 3) Jakob T, 3) Köllisch G, 1) Sandholzer N, 4) Soewarto D, 1) Krebs O, 5) Kremmer E, 4) Hrabe de Angelis M, 6) Balling R, 7) Pfeffer K, 1) Wolf E
Institutions: 1) Institute of Molecular Animal Breeding, Gene Center, Feodor-Lynen-Str. 25 82377 München, Germany. 2) Institute for Medical Microbiology, Technische Universität München, Troger Str. 4a, 81675 München, Germany. 3) Division Environmental Dermatology and Allergology, GSF-TUM, Ingolstädter Landstr. 1 85764 Neuherberg, Germany. 4) Institute of Experimental Genetics, GSF Research Center for Environment and Health, Neuherberg, Germany. 5) Institute of Molecular Immunology GSF Research Center for Environment and Health Marchionistr. 25, 81377 München, Germany. 6) Gesellschaft für Biotechnologische Forschung mbH, Mascheroder Weg 1, 38124 Braunschweig, Germany. 7) Institute for Med. Microbiology, Heinrich Heine Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf

Analysis of gene function in vivo is mostly performed by transgenic insertion, gene inactivation by homologous recombination in embryonic stem cells and gene trapping. We have complemented this approach by a genome wide chemical mutagenesis in mice using ethyl-nitrosourea (ENU), followed by subsequent phenotype specific screening.

We used ELISA to identify mutants with elevated levels of rheumatoid factor and anti-DNA antibodies. ELISA was also used to identify deviations in the basal level of single or multiple immunoglobulin isotypes.

Employing flow cytometry we screened for mouse mutants in which the percentage of defined cell types or the expression level of relevant cell surface proteins is altered.

Until to date we have recovered and genetically confirmed more than 70 mutant mouse lines with phenotypes ranging from modest increase of single immunoglobulin isotypes to the complete loss of B- and T-cells. Identification of the respective mutation is pursued by outcross to a second inbred line followed by an intracross and subsequent polymormhic Mit marker (Massachusetts Institute of Technology) analysis.

Here we report on a series of recessive mouse lines in which B- and/or T-cell development or function is severely compromised as well as on a mouse line with elevated plasma IgA accompanied by a high incidence of chronic diarrhea. These mouse lines can serve as models for human diseases and help to unravel the function of the respective genes.


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