International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 97 - NOVEL MOUSE MODELS OF DIABETES MELLITUS -- IDENTIFICATION, MAPPING AND CHARACTERIZATION OF MUTANTS FROM THE RIKEN ENU MUTAGENESIS PROJECT

Inoue M
Mouse Functional Genomics Research Group, RIKEN Genomic Sciences Center GSC)

Co-Authors: 2) Sakuraba Y, 1) Motegi H, 1) Matsui J, 1) Toki H, 3) Shigeyama Y, 4) Kubota N, 1) Kaneda H, 1) Ishijima J, 1) Adachi T, 1) Kagami T, 1) Inoue A, 1) Wakana S, 2) Gondo Y, 1) Minowa O, 1) Shiroishi T, 1) Noda T
Institutions: 1) Mouse Functional Genomics Research Group, RIKEN Genomic Sciences Center GSC), 2) Population and Quantitative Genomics Team, RIKEN GSC, 3) Kobe University, 4) University of Tokyo

Various visible, clinical biochemical, and hematological phenotypes as well as cardiovascular anomalies, hearing abnormalities, and tumorigenesis are studied in the RIKEN mouse mutagenesis project. One specific aim of our project is to generate diabetic models that will enable us to clarify the functions of genes and the pathogenic mechanisms of human diabetes. Of the 10,000 F1 offspring of mutagenized C57BL/6J male mice crossed to DBA/2J females screened using a clinical biochemical test, we isolated 82 hyperglycemic outliers. For inheritance testing and mapping, we backcrossed the F1 outliers to the DBA/2J animals and recovered the N2 progeny. To further analyze the phenotype of these progeny, we performed the oral glucose tolerance test (OGTT) and the insulin tolerance test (ITT). Of the 82 hyperglycemic outliers, 54 were subjected to inheritance testing: 20 lines displayed hereditary hyperglycemia, 20 did not have hereditary hyperglycemia and 14 are still being tested. Mapping analysis with SNP markers and microsatellite markers of the inherited mutant lines revealed that some mutations were linked on several chromosomes. Candidate gene analysis of the mapped lines identified mutations in several mutant lines that appear to be alleles with one another. Further information will be presented on the details of the phenotypes and candidate genes under investigation.


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