alternative splicing in mouse kidney: regulation during development and by dietary K intake.

The pore-forming α-subunit of the large-conductance K (BK) channel is encoded by a single gene, BK channel-mediated K secretion in the kidney is crucial for overall renal K homeostasis in both physiological and pathological conditions. BK channels achieve phenotypic diversity by various mechanisms, including substantial exon rearrangements at seven major alternative splicing sites. However, alternative splicing in the kidney has not been characterized. The present study aims to identify the major splice variants of mouse in whole kidney and distal nephron segments. We designed primers that specifically cross exons within each alternative splice site of mouse and performed real-time quantitative RT-PCR (RT-qPCR) to quantify relative abundance of each splice variant. Our data suggest that splice variants within mouse kidney are less diverse than in the brain. During postnatal kidney development, most splice variants at site 5 and the COOH terminus increase in abundance over time. Within the kidney, the regulation of alternative exon splicing within these two sites by dietary K loading is both site and sex specific. In microdissected distal tubules, the alternative splicing profile, as well as its regulation by dietary K, are distinctly different than in the whole kidney, suggesting segment and/or cell type specificity in splicing events. Overall, our data provide evidence that alternative splicing is regulated during postnatal development and may serve as an important adaptive mechanism to dietary K loading in mouse kidney. We identified the major splice variants that are specifically expressed in the whole mouse kidney or aldosterone-sensitive distal nephron segments. Our data suggest that alternative splicing is developmentally regulated and subject to changes in dietary K.