An important consideration of any experiment using a constitutive knockout model is that compensatory changes may take place in response to the deletion, potentially causing changes in receptor function that will have occurred throughout the brain and during development and may be responsible for the resulting changes in phenotype. Certainly, in the case of deletion of the gabra1 gene resulting in loss of the α1-subunit, there is evidence for increased expression of α2- and α3-subunits, and decreased expression of γ2-subunits, as well as alterations in receptor clustering and distribution [42], [43] and in various other genes involved in neural plasticity [44]. Using quantitative PCR analysis, we found no evidence for altered expression of other GABAA receptor subunits in the KO [10], indicating a lack of compensation in subunit expression at the transcription level in the adult mouse. Nevertheless we cannot exclude changes either at the protein level, or patterns of insertion of receptors into the membrane, or to other neurotransmitter systems.
