We describe the generation of transgenic mouse lines expressing the Cre recombinase enzyme in brain under control of the CamKII alpha. gene present in a BAC expression vector. The CamKII alpha BAC transgene gave a faithful expression pattern resembling the pattern of the endogenous CamKII alpha gene. Specifically, high levels of CamKII alpha Cre were detected in hippocampus, cortex, and amygdala, and lower levels were detected in striatum, thalamus, and hypothalamus. As expected, no expression was detected in the cerebellum or outside of the brain. The expression level of the BAC CamKII alpha. driven Cre was shown to be copy number dependent. To test the activity of the Cre recombinase, the transgenic mice were crossed with mice harbouring the CREB (cAMP response element binding protein) allele with the 10th exon flanked by two IoxP sites, and recombination was monitored by the disappearance of the CREB protein. Finally, evaluation of the developmental postnatal expression of the CamKII alpha Cre BAC revealed the expression of the Cre recombinase as early as P3. (C) 2001 Wiley-Liss, Inc.