Traditional methods for testing gene function in mice have relied on the use of constitutive and conditional gene knockouts and classical transgenic animals. Producing these mice is expensive and time-consuming, and may not yield an easily interpretable behavioral phenotype due to potential developmental compensations from the complete loss of gene function. In addition to the relative ease and speed of their generation, mice with gene knockdown by shRNA may be advantageous, as gene function is not completely eliminated, thus circumventing potential lethality associated with null alleles as well as the above-mentioned compensatory mechanisms. By utilizing transgenic mice expressing lentiviral-delivered shRNAs, animals with different degrees of gene knockdown can be produced rapidly as a screening tool to complement the generation of traditional gene knockout animals. As we have done here, founder mice may be examined for correlations in behavioral responses to ethanol as a first determinant of whether a gene may play a role in alcoholrelated behaviors.
