Alternative mRNA splice variants of the rat CIC-2 chloride channel gene are expressed in lung: genomic sequence and organization of CIC-2

The CIC-2 epithelial cell chloride channel is a voltage-, tonicity-and pH-regulated member of the CIC super family, We have previously shown that rat lung CIC-2 (rCIC-2) is down-regulated at birth, and molecular diversity is generated by alternative splicing [Murray et al. (1995) Am. J. Respir. Cell Mel. Biol. 12, 597-604; Murray et al. (1996) Am. J. Physiol, 271, L829-L837; Chu et al, (1996) Nucleic Acids Res. 24, 3453-3457]. To investigate other possible mRNA splice variations, we sequenced the entire rCIC-2 gene and found that CIC-2Sa (formerly CIC-SS) results from the deletion of exon 20. The preceding intron 19 has an unusually high CT content and a rare AAG acceptor site, Because both features were also found in intron 13, we next tested the hypothesis that intron 13 would be involved in alternative splicing, As predicted, a second splice product, CIC-2Sb, was found by RT-PCR, but only in lung. When we compared the genomic maps of rCIC-2 and human CIC-1 (hCIC-1), striking similarities were found in each exon except for rCIC-2 exon 20, which is absent in hCIC-1. These observations suggest that CIC-1 and CIC-2 may have evolved by gene duplication, mutation and DNA rearrangement.