Conditional gene knockout

Conditional gene knockout aka "conditional sequence deletion" or short: "conditional deletion", is a relatively new technique of genetic engineering, an offshoot of gene knockout technology where a specific target gene is eliminated from a single organ in the body of an experimental animal, rather than the whole body, as conventional gene knockout technology would entail. It can be applied to eukaryotic and prokaryotic systems. This allows for more sophisticated experiments.

Technique

The most commonly used technique is using the Cre-Lox recombination system, described 1995[1] The enzyme Cre recombinase is a site-specific recombinase, which means it is promoting recombination by recognizing a short and specific nucleotide sequence without any added factor. Cre recombinase is known to be expressed in only a few cell types. Hence the researcher would be able to decide where exactly the gene in question is to be knocked out, thus allowing for a greater degree of freedom and scientific accuracy.

When publications are searched on Pubmed using the terms 'conditional sequence deletion' publication numbers have increased from initially in the teens per year during the late nineties to now well over 100 publications per year.[2]

Advantages

A main advantage conferred by this technique is the increased precision of the knock out, creating a so called 'clean' mutation (ie devoid of selectable markers) and thus observation and analysis. Also, such genetically modified mice are able to survive longer.

Examples

A specific gene in mouse brain thought to be involved in the onset of Alzheimer's disease which codes for the enzyme cyclin-dependent kinase 5 (Cdk5) was knocked out. Such mice were found to be 'smarter' than normal mice and were able to handle complex tasks more intelligently compared to 'normal' mice bred in the laboratory.[3]


References

  1. ↑ Plück A. Conditional mutagenesis in mice: the Cre/loxP recombination system.Int J Exp Pathol. 1996 Dec;77(6):269-78.
  2. ↑ http://www-ncbi-nlm-nih-gov/pubmed/?term=conditional+sequence+deletion
  3. ↑ "Increased intelligence through genetic engineering". 2007-05-29. Retrieved 2007-11-07.