Genetic knockout analysis

Keywords Elementary mode analysis Engineering Genetic knockout analysis Metabohc minimal metabolic functionality Rational strain design... 

Mutant or knockout mice defective in specific enzymes involved in lipid synthesis have provided powerful tools for genetic analysis of lipid function in the nervous system. For example, disruption of the genes for ceramide galactosyl transferase or galactosyl ceramide sulfotransferase,... 

The second area worthy of comment is with regard to assignment of enzyme function based on amino acid sequence alone. In some cases sequence comparisons can be used to determine if a new cDNA encodes one of the well-known flavonoid biosynthetic enzymes. However, in some cases, sequence similarity is insufficient for reliable prediction of the encoded function. For example, the OMTs may have amino acid identities of above 85% but different activities. For transcription factors such sequence-based assignments of function are significantly more difficult, as specific roles for a given factor may have arisen in particular species. Thus, analysis of genetic mutants and transgenic overexpression or knockout lines is still preferable for confirmation of the encoded activities. 

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. 

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