title: The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.
abstract: The aquaporin family of membrane water transport proteins are expressed in diverse tissues, and in brain the predominant water channel protein is AQP4. Here we report the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Two cDNAs were isolated corresponding to the two initiating methionines (M1 in a 323-aa polypeptide and M23 in a 301-aa polypeptide) previously identified in rat [Jung, J.S., Bhat, R.V., Preston, G.M., Guggino, W.B. & Agre, P. (1994) Proc. Natl. Acad. Sci. USA 91, 13052-13056]. Similar to other aquaporins, the AQP4 gene is composed of four exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. Transcription initiation sites have been mapped in the proximal promoters of exons 0 and 1. RNase protection revealed distinct transcripts corresponding to M1 and M23 mRNAs, and AQP4 immunoblots of cerebellum demonstrated reactive polypeptides of 31 and 34 kDa. Using a P1 and a lambda EMBL subclone, the chromosomal site of the human AQP4 gene was mapped to chromosome 18 at the junction of q11.2 and q12.1 by fluorescence in situ hybridization. These studies may now permit molecular characterization of AQP4 during human development and in clinical disorders.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.forename: M D
authors.initials: MD
authors.lastname: Lee
authors.forename: B L
authors.initials: BL
authors.lastname: Smith
authors.forename: J S
authors.initials: JS
authors.lastname: Jung
authors.forename: P
authors.initials: P
authors.lastname: Agre
authors.forename: M A
authors.initials: MA
authors.lastname: Verdijk
authors.forename: G
authors.initials: G
authors.lastname: Merkx
authors.forename: J P
authors.initials: JP
authors.lastname: Rijss
authors.forename: P M
authors.initials: PM
authors.lastname: Deen
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins; D001483:Base Sequence; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D005796:Genes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D007473:Ion Channels / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D014158:Transcription, Genetic
chemical_list: C496030:AQP4 protein, human; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D018076:DNA, Complementary; D007473:Ion Channels; D012333:RNA, Messenger