Further dissection of a genomic locus associated with behavioral activity in the Wistar-Kyoto hyperactive rat, an animal model of hyperkinesis.
Mol Psychiatry. 2003-01-01; 8(3): 348-352
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1. Mol Psychiatry. 2003 Mar;8(3):348-52.
Further dissection of a genomic locus associated with behavioral activity in the
Wistar-Kyoto hyperactive rat, an animal model of hyperkinesis.
Moisan MP(1), Llamas B, Cook MN, Mormède P.
(1)Laboratory of Neurogenetics & Stress, INSERM U471-INRA UR 502, Institut
François Magendie, Bordeaux, France.
Molecular genetic studies of attention-deficit hyperactivity disorder (ADHD) are
a major focus of current research since this syndrome has been shown to be highly
heritable.(1) Our approach has been to search for quantitative trait loci (QTL)
in a genetic animal model of hyperkinesis, the Wistar-Kyoto hyperactive (WKHA)
rat, by a whole-genome scan analysis. In a previous article, we reported the
detection of a major QTL associated with behavioral activity in an F2 cross
between WKHA and Wistar-Kyoto (WKY) rat strains.(2) Here, we extend our analysis
of this cross by adding new genetic markers, now defining a 10 cM interval on rat
chromosome 8 associated with ambulatory and exploratory activities. Then we
present a replication of this QTL detection, at least for exploratory activity,
by a new genetic mapping analysis of an activity QTL in an F2 cross between the
WKHA and Brown Norway (BN) rat strains. Overall, the results provide compelling
evidence for the presence of gene(s) influencing activity at this locus. The QTL
interval has been refined such that the human orthologous region could be defined
and tested in human populations for association with ADHD. Ultimately, the
improved dissection of this genomic locus should allow the identification of the
PMID: 12660808 [Indexed for MEDLINE]