Mouse water channel aquaporin 4: gene and cdna cloning and structure analysis

The goal of this study was to examine the regulation and gene structure of AQP4, the water channel that is expressed in brain, lung and kidney. We found that AQP4 expression is developmentally regulated in all tissues. In the lung AQP4 mRNA is transiently increased around birth, indicating its role for lung water clearance, and is inducible by glucocorticoids and 3 -adrenergic agonists. In the brain AQP4 may play a role as an osmoreceptor. We have screened a eDNA library from mouse embryonic brain and mouse genomic library, cloned eDNA and AQP4 gene and found alternative splicing and different starts of transcription. The shorter form of mRNA has another reading frame (from Leu113), which codes for a protein with unknown function. AQP1 gene restriction mapping and partial sequencing of promoters and coding regions demonstrate alternative start of transcription at +3 kb position before beginning of AQP4 translation and the presence of the putative reglJlatory elements AP1, c-Jun and CTF/NF-I. The exon-intron boundaries of the mouse AQP4 gene were identified and target vectors and clones of embryonic stem cells as first step of knockout model generation have been prepared. This study was supported by grants from Swedish Medical Council, the Swedish ttear and Lung Foundation, the Nov() Nordisk Foundation and Karen Elise Jensen foundation. S.Zelenin was supported by Wenner Gren center Foundation.