DISTRIBUTION OF CALCINEURIN-A ISOENZYME MESSENGER-RNAS IN RAT THYMUS AND KIDNEY

The distribution of the mRNAs encoding the different isoforms of the catalytic subunit (A subunit) of calcineurin has been investigated in rat thymus and kidney using in situ hybridization histochemistry with specific antisense oligonucleotide probes. In the thymus, the mRNAs of the A beta isoforms were the predominant transcripts and showed very intense hybridization signals in the cortical areas. The A alpha mRNAs were expressed at low levels. A beta 2 mRNA was expressed at higher levels than A beta 3 mRNA, but no difference could be detected between the expression levels of A alpha 1 and A alpha 2. In the kidney, highest calcineurin A mRNA hybridization signals were found in the medulla. Signal intensities of A alpha mRNAs were comparable to those of A beta mRNAs. A alpha 1 mRNA level was extremely weak, and A beta 2 mRNA expression was slightly higher than A beta 3 mRNA expression. A tissue-specific distribution pattern of the alternatively spliced isoforms of calcineurin A, as suggested by these preliminary data from thymus and kidney, may be critical in understanding the toxic side-effects associated with the use of the immunosuppressive, calcineurin-inhibiting compounds cyclosporin A and FK506.