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)
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.
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.