International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 180 - MOUSE MUTANTS WITH HYPERACTIVITY: RECENT PROGRESS IN RIKEN ENU-MUTAGENESIS PROJECT

Wada Y 1, Masuya H 1, Kushida T 1, Kawai A 1, Nishii R 1, Miura I 1, Furuse T 1, Kobayashi K 1, Kaneda H 1, Suzuki T 1, Minowa O 1, Gondo Y 2, Noda T 1, Wakana S 1, Shiroishi T 1

1 Mouse Functional Genomics Research Group, RIKEN GSC, Tsukuba, Japan, 2 2Population and Quantitative Genomics Team, RIKEN GSC, Yokohama, Japan

Recent studies have demonstrated that psychiatric diseases such as schizophrenia and bipolar disorder have some genetic basis. In human populations, however, identification of genes underlying psychiatric disorders is still difficult because of polygenic inheritance and gene-environment interactions. Genetic studies using mouse models have great advantage for identification of molecular pathways of behavior. In order to establish mouse mutants modeling symptoms of psychiatric disorders, we have initiated dominant behavioral screening in RIKEN ENU-mutagenesis project. One of our focuses was “increased locomotor activity” in a novel and/or familiar environment, because hyperactivity in mice has been associated with behavioral symptoms of several human psychiatric disorders; e.g., hyperactivity in attention-deficit hyperactivity disorder (ADHD), and psychomotor agitation in schizophrenia and mania. We have screened about 1,500 G1 animals (DBA/2J x mutagenized C57BL/6J) for home-cage activity, and 2,000 G1s for open-field activity. Thirty phenodeviants with hyperactivity (home-cage 8; open-field 22) were detected and mated with DBA/2J for inheritance testing. Heritability of the seven lines (home-cage 1; open-field 6) was confirmed. They were hyperactive only in either home-cage or open-field, but two open-field mutant lines, M100073 and M100174, showed hyperactivity both in home-cage and open-field. Percentages of hyperactive offspring in N2 progenies were 20-50%, but in the N3 progenies, the percentages were decreased to 3-8 % except in M100073 and M100174. The responsible genes of M100073 and M100174 were mapped to Chr.6 and Chr.2, and fine mapping is underway. We will report the recent progress of gene mapping and behavioral characterization focusing on ADHD and schizophrenia.

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