International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Wakana S
Mouse Functional Genomics Research Group, RIKEN GSC

Co-Authors: 1) Wada Y, 1) Masuya H, 1) Kaneda H, 1) Ishijima J, 1) Kobayashi K, 1) Kawai A, 1) Kushida T, 1) Nishii R, 2) Gondo Y, 1) Noda T, 1) Shiroishi T
Institutions: 1) Mouse Functional Genomics Research Group, RIKEN GSC. 2) Population and Quantitative Genomics Team, RIKEN GSC

A Attention deficits and hyperactivity disorder (ADHD) is a common behavioral disorder affecting 5% school-aged population. The main symptoms of ADHD are persistent inattention and/or hyperactive-impulsive behavior, which cause impaired social and/or academic functioning as a result. Family and twin studies have revealed that ADHD has genetic basis. Association and linkage of ADHD with D4, D2 and D5 dopamine receptor genes (DRD4, DRD2, and DRD5), dopamine transporter gene (DAT1), and dopamine beta hydroxylase gene (DBH) have been suggested. However, no genes involved in ADHD have been unambiguously identified. ADHD relevant behavioral abnormality is one of the targets of ENU mutagenesis program in RIKEN GSC. Behavioral traits of mice, relevant to ADHD, are (1) increased locomotor activity in open field and home cage, and (2) paradoxical calming effects of psychostimulants such as methylphenidate on hyperactivity. We have screened 1,354 G1 animals in home-cage activity test and 2,023 animals in open-field test for the dominant behavioral phenotypes, and detected one mutant in home-cage and six mutants in open-field with hyperactivity. Two of six open-field mutants, M100073 and M100174, showed hyperactivity both in home-cage and open-field. Because this phenotype parallels that of ADHD, we are now testing the effects of methylphenidate on hyperactivity to examine paradoxical calming effect in these two mutants. M100073 was mapped to Chr.6, and M100174 was mapped to Chr.2. Further gene mapping and behavioral characterization focusing on ADHD relevant abnormalities, e.g. learning deficit or inattention, are in progress using backcrossed progenies.

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