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The cystic fibrosis transmembrane conductance regulator is encoded by the gene known to be mutated in patients with cystic fibrosis. This paper reports the cloning and sequencing of cDNAs for the murine homolog of the human cystic fibrosis transmembrane conductance regulator gene. A clone that, by analogy to the human sequence, extends 3' from exon 9 to the poly(A) tail was isolated from a mouse lung cDNA library. cDNA clones containing exons 4 and 6b were also isolated and sequenced, but the remainder of the mRNA proved difficult to obtain by conventional cDNA library screening. Sequences spanning exons 1-9 were cloned by PCR from mouse RNA. The deduced mouse protein sequence is 78% identical to the human cystic fibrosis transmembrane regulator, with higher conservation in the transmembrane and nucleotide-binding domains. Amino acid sequences in which known cystic fibrosis missense mutations occur are conserved between man and mouse; in particular, the predicted mouse protein has a phenylalanine residue corresponding to that deleted in the most common human cystic fibrosis mutation (delta F508), which should allow the use of transgenic strategies to introduce this mutation in attempts to create a "cystic fibrosis mouse".

Type

Journal article

Journal

Genomics

Publication Date

06/1991

Volume

10

Pages

301 - 307

Keywords

Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Cloning, Molecular, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, DNA, Gene Library, Humans, Membrane Proteins, Mice, Molecular Sequence Data, Oligonucleotides, Polymerase Chain Reaction, Sequence Alignment