Two lines of transgenic mice expressing cre-recombinase exhibit increased seizure susceptibility

Abstract

Conditional mouse models based on the Cre-recombinase (Cre)-loxP method are a powerful tool for determining the spatial and temporal function of genes in neuroscience research. The Emx1-Cre conditional model is designed to drive Cre expression in a predominantly excitatory neuron specific manner and the Dlx5/6-Cre mouse expresses Cre predominantly in cortical inhibitory neurons. The mouse models expressing the Cre transgene are healthy, active and have no overt behavioural or brain histological phenotypes. Subcutaneous pentylenetetrazol (scPTZ) is a proconvulsant frequently used to probe neuronal network excitability. In both the Emx1-Cre and Dlx5/6-Cre conditional mouse models the latency to scPTZ-induced seizures was significantly shorter than for their wild-type littermates. This shows that mouse models carrying the Cre transgene alone can have significant behavioural phenotypes. This may act as a confound to the interpretation of data obtained from crosses with loxP-flanked targets especially in the context of epilepsy phenotypes. These data highlight that appropriate control experiments that compare wild-type mice to those that carry the cre-transgene but not the loxP-flanked target are essential when using this method.