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

The distribution of the mRNAs encoding the different isoforms of the c atalytic subunit (A subunit) of calcineurin has been investigated in r at thymus and kidney using in situ hybridization histochemistry with s pecific antisense oligonucleotide probes. In the thymus, the mRNAs of the A beta isoforms were the predominant transcripts and showed very i ntense hybridization signals in the cortical areas. The A alpha mRNAs were expressed at low levels. A beta 2 mRNA was expressed at higher le vels than A beta 3 mRNA, but no difference could be detected between t he expression levels of A alpha 1 and A alpha 2. In the kidney, highes t 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 exp ression was slightly higher than A beta 3 mRNA expression. A tissue-sp ecific distribution pattern of the alternatively spliced isoforms of c alcineurin A, as suggested by these preliminary data from thymus and k idney, may be critical in understanding the toxic side-effects associa ted with the use of the immunosuppressive, calcineurin-inhibiting comp ounds cyclosporin A and FK506.