Recombinant or transgenic non-human mammals are described having a mutant
tryptophan hydroxylase 2 (Tph2) gene resulting in altered synthesis of
5-hydroxytryptophan and serotonin in the brain. In some embodiments the
mutant tryptophan hydroxylase 2 gene contains mouse R439H and/or P447R
functional mutations, or their corresponding mutations in other species.
Congenic non-human mammals having mutant tryptophan hydroxylase 2 genes
are also provided. Methods of screening a compound for serotonergic
activity or activity in treating a serotonergic neurotransmission
dysregulation disorder are provided, which include administering a test
compound to a recombinant non-human mammal and then detecting the
presence or absence of serotonergic activity, or activity in treating a
serotonergic neurotransmission dysregulation disorder, in the mammal. A
cell such as a nerve cell (e.g., a central nervous system neuron)
isolated from a transgenic or congenic mammal is also disclosed, along
with cell cultures containing these cells. Such mammals and cells and
cell cultures are useful in vitro for screening the activity of candidate
compounds for their effect on serotonergic neurotransmission and for
their activity in treating serotonergic neurotransmission dysregulation
disorders.