Transgenics and knockouts

The last decade has provided new molecular and genetic tools for the analysis of changes in the dopamine turnover, particularly in the generation of strains of knockout mice that are deficient in various aspects of dopamine neurone development, in the cellular machinery for dopamine neurotransmission, or in other genes associated with parkinsonism in man. As several good recent reviews are available (Jankowsky et al., 2002 Eells, 2003), the present account will focus on the behavioral phenotypes associated with genetic manipulation of dopamine systems of the forebrain. 

Dopamine synthesis and turnover. Rather than disrupting the specification of presumptive dopamine neurones per se, an alternative strategy is to knockout key components of the cellular synthesis of dopamine production or turnover. As the rate limiting enzyme in dopamine synthesis is TH, TH knockouts offer an obvious strategy. However, deletion of the TH gene effects adrenergic, including sympathetic as well as 

Knockout of different components of the dopamine processing machinery of cells influences the susceptibility of mice to a variety of toxins. Thus, DAT / mice show a reduced sensitivity to MPTP (Gainetdinov et al,. 1997) whereas VMAT+/ mice exhibit an enhanced sensitivity to the toxicity of MPTP and amphetamine (Takahashi et al., 1997 Gainetdinov et al., 1998 Fumagalli et al., 1999) but not to l-DOPA (Reveron et al., 2002). 

Mice with deletion of the D2 receptors have typically exhibited more marked behavioral debility, including reduced locomotion and rearing, catalepsy akin to the 

Behavioral effects of transgenic mice that overexpress other parkin genes associated with familial PD are yet to be reported. 

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Crawley, J. N. (2007) What s wrong with my mouse Behavioural phenotypying of transgenic and knockout mice, 2nd ed. John Wiley Sons, Inc., New Jersey. 

Key Words Transgenic and knockout mice neuropsychiatric disorders anxiety the neural circuitry of complex behavior SERT Pet-1 tryptophan hydroxylase 2. 

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Transgenic and knockout mice which develop metastases... 

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In addition to the controlled expression of genes made possible by available expression systems and siRNA, specific control of gene expression in the whole animal has been made possible by recombinant DNA technology. These transgenic and knockout animals have been invaluable in the dissection of a number of important toxicological pathways, and are discussed further elsewhere in the encyclopedia. 

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