Crossing Cacna1etm1Tsch mice with a strain expressing Cre ubiquitously resulted in the excision of exon 2, which encodes the first transmembrane segment of domain 1 and the adjacent loop to IS2. RT-PCR analysis revealed a different splice pattern for exon 1 than expected, producing a novel second exon of 204 bp that contained an in-frame stop codon. Western blot analysis of mutant brain microsomal membranes detected no protein expression from any Cacna1e subunit.