An approximate 12 kb genomic region containing exon 2 was replaced with a neomycin-resistance cassette in the opposite transcriptional orientation of the endogenous gene. RT-PCR analysis confirmed the presence of an exon 2 deleted transcript and Western blot shows the expression of a truncated protein. The deletion of exon 2 which contains the coiled-coil domain results in increased CREB1 transcriptional activity.