TY - JOUR
T1 - Alternative mRNA splice variants of the rat ClC-2 chloride channel gene are expressed in lung
T2 - Genomic sequence and organization of ClC-2
AU - Chu, Shijian
AU - Zeitlin, Pamela L.
N1 - Funding Information:
We thank Dr Carol B. Murray for very helpful discussions on this project. We also thank Minzhi M. Liu for excellent technical assistance. This work was supported by R29 HL48274 to P.L.Z. and a Cystic Fibrosis Foundation Fellowship to S.C.
PY - 1997/10/15
Y1 - 1997/10/15
N2 - The ClC-2 epithelial cell chloride channel is a voltage-, tonicity- and pH-regulated member of the ClC super family. We have previously shown that rat lung ClC-2 (rClC-2) is down-regulated at birth, and molecular diversity is generated by alternative splicing. To investigate other possible mRNA splice variations, we sequenced the entire rClC-2 gene and found that ClC-2Sa (formerly ClC-2S) 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, ClC-2Sb, was found by RT-PCR, but only in lung. When we compared the genomic maps of rClC-2 and human ClC-1 (hClC-1), striking similarities were found in each exon except for rClC-2 exon 20, which is absent in hClC-1. These observations suggest that ClC-1 and ClC-2 may have evolved by gene duplication, mutation and DNA rearrangement.
AB - The ClC-2 epithelial cell chloride channel is a voltage-, tonicity- and pH-regulated member of the ClC super family. We have previously shown that rat lung ClC-2 (rClC-2) is down-regulated at birth, and molecular diversity is generated by alternative splicing. To investigate other possible mRNA splice variations, we sequenced the entire rClC-2 gene and found that ClC-2Sa (formerly ClC-2S) 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, ClC-2Sb, was found by RT-PCR, but only in lung. When we compared the genomic maps of rClC-2 and human ClC-1 (hClC-1), striking similarities were found in each exon except for rClC-2 exon 20, which is absent in hClC-1. These observations suggest that ClC-1 and ClC-2 may have evolved by gene duplication, mutation and DNA rearrangement.
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U2 - 10.1093/nar/25.20.4153
DO - 10.1093/nar/25.20.4153
M3 - Article
C2 - 9321672
AN - SCOPUS:0030753177
SN - 0305-1048
VL - 25
SP - 4153
EP - 4159
JO - Nucleic acids research
JF - Nucleic acids research
IS - 20
ER -