THE HUMAN AQUAPORIN-5 GENE - MOLECULAR CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION

The cDNA for the fifth mammalian aquaporin (AQP5) was isolated from ra t, and expression was demonstrated in rat salivary and lacrimal glands , cornea, and lung (Raina, S., Preston, G. M., Guggino, W. B., and Agr e, P. (1995) J. Biol. Chem. 270, 1908-1912). Here we report the isolat ion and characterization of the human AQP5 cDNA and gene. The AQP5 cDN A from a human submaxillary gland library contains a 795-base pair ope n reading frame encoding a 265-amino acid protein. The deduced amino a cid sequences of human and rat AQP5 are 91% identical with 6 substitut ions in the 22-amino acid COOH-terminal domain. Expression of human AQ P5 in Xenopus oocytes conferred mercurial-sensitive osmotic water perm eability (Pf) equivalent to other aquaporins. The human AQP5 structura l gene resides within a 7.4-kilobase SalI-EcoRI fragment with four exo ns corresponding to amino acids 1-121, 122-176, 177-204, and 205-265 s eparated by introns of 1.2, 0.5, and 0.9 kilobases. A transcription in itiation site was identified 518 base pairs upstream of the initiating methionine. Genomic Southern analysis indicated that AQP5 is a single copy gene which localized to human chromosome 12q13; this coincides w ith the chromosomal locations of the homologous human genes MIP and AQ P2, thus confirming 12q13 as the site of an aquaporin gene cluster. Th e mouse gene localized to distal chromosome 15. This information may p ermit molecular characterization of AQP5 expression during normal deve lopment and in clinical disorders.