Using viral vectors to study local gene function in the mouse brain

In recent years genetic tools that influence the expression of candidate genes in a conditional manner have become increasingly important. This is particularly true for brain research since we know that the brain is an extremely heterogenous tissue. The use of the established transgenic mouse lines which express cre recombinase under conditional promoters have adressed this issue and resulted in important new insights. Nevertheless, only a limited number of brain specific cre mouse lines are available and none of them are restricted to a specific brain structure which might be helpful to elucidate the etiology of brain diseases. To overcome these obstacles we additionally aim to use adeno-associated virus (AAV)-based vectors for functional genetic studies. The advantages of this system are the rapid production of altered gene expression in the brain but also a high flexiblity and specificity to target brain structures. Two loss of function approaches are applied using viral vectors: On the one hand we express short hairpin transcripts (shRNAs) in order to trigger RNA-interference (RNAi) which results in a specific gene knock-down. On the other hand we have the possibilty to inject cre recombinase expressing vectors into the brains of our transgenic mouse lines. Recombination leads to a conditional gene knock-out. We are currently evaluating the potency of these new tools on the molecular level and testing if the loss of gene function leads to a behavioural phenotype.