Openness (Novelty-Seeking, Fear)

bcl-2 [GE]
    Over-expression of the human bcl-2 gene in mice results in reduced fear, neophobia, and anxiety in adult mice.  Rondi-Reig et al., Neuroreport, 8:2429-2432, 1997.

calmodulin (alpha-calcium-calmodulin-dependent kinase II, CaMKII) [GE]
    Mice deficient in the calmodulin gene (alpha-calcium-calmodulin-dependent kinase II, CaMKII) were engineered.  Heterozygotes showed a decreased fear response and and increase in defensive aggression.  The homozygote were abnormal in all behavioral paradigms tested.  Chen et al., Science, 266:291-294, 1994.

dopamine transporter (DAT) [GE]
    Knockout mice lacking the gene coding for the plasma membrane dopamine transporter (DAT) are hyperactive.  This activity was exacerbated by exposure to a novel environment, suggesting that the DAT knockout mice might be less able to adapt to novel stimuli than wild-type controls.  Agents that increased serotonergic neurotransmission were found to decrease hyperactivity in knockout mice.  Parallels between the knockout mice and individuals with attention-deficit hyperactivity disorder (ADHD) suggest that these mice may serve as a useful animal to test new therapies and provide insights into hyperactivity disorders.  Gainetdinov et al., Science, 283:397-401, 1999.

Novelty-seeking
cannabinoid (CB1) receptor [GE]
    The time spent in exploring unknown objects was significantly increased in mice lacking a functional CB1 receptor.  Ledent et al., Science, 283:401-404, 1999.

dopamine receptor, subtype DR4 (DR4)+ [HGL]
    The association between a polymorphism in exon III of the dopamine receptor DR4 and novelty-seeking behavior in Japanese women was investigated.  The long allele (greater than 5 repeats) was associated with significantly elevated novelty seeking scores, including extravagance and exploratory excitability.  Tomitaka et al., Am. J. Med. Genet., 88:469-471, 1999.  Higher novelty-seeking scores were also associated with a polymorphism of the promoter region of DR4 in a Japanese population.  This polymorphism was shown to effect the expression of the DR4 gene in tissue culture cells.  Okuyama et al., Mol. Psychiatry, 5:64-69, 2000.  This polymorphism was also shown to affect novelty-seeking scores for females, but not males, in a Caucasian population.  Ronai et al., Mol. Psychiatry, 6:35-38, 2001.  However, other studies have been unable to replicate these results.  See, e.g., Paterson et al., Neuropsychopharmacology 21(1):3-16, 1999.