At about the same time, three groups independently reported the generation of VMAT2 KO mice (Fon, et al., 1997; Takahashi, et al., 1997; Y. M. Wang, et al., 1997), demonstrating very similar patterns of effects. Perhaps not surprisingly, given the potential impact of VMAT2 deletion on all monoaminergic neurotransmission, deletion of both copies of VMAT2 was mostly lethal within a few days after birth and completely lethal by 2 weeks of age, due to substantially reduced feeding behavior (indeed general reductions in behaviour overall). Homozygous VMAT2 KO mice had very low whole brain monoamine levels despite increased synthesis rates (Fon, et al., 1997; Y. M. Wang, et al., 1997). Heterozygous KO mice were shown to have somewhat reduced monoamine levels and reduced exocytotic release (Fon, et al., 1997; Takahashi, et al., 1997; Y. M. Wang, et al., 1997), although the extent of these reductions differed by brain region and neurotransmitter across the three reports. Indeed, Takahashi et al. (1997) found elevated levels of both dopamine and DOPAC in the striatum, although this was in the context of a variety of
