DIFFERENTIAL CNS EXPRESSION OF ALTERNATIVE MESSENGER-RNA ISOFORMS OF THE MAMMALIAN GENES ENCODING CAMP-SPECIFIC PHOSPHODIESTERASES

To study alternative splicing and tissue-specific expression of the ma mmalian genes encoding type-IV cAMP-specific phosphodiesterases, which are homologs of the dnc learning and memory gene of Drosophila melano gaster, we cloned seven cDNAs from four rat loci (PDE1, PDE2, PDE3 and PDE4) homologous to dnc. The deduced amino-acid sequences of the prot eins encoded by the rat loci were shown to have a 1:1 correspondence w ith those encoded by the four human dnc homologs. The proteins encoded by at least one cDNA from each of the four rat loci contained novel N -terminal upstream conserved regions (UCR1 and UCR2), described previo usly in proteins encoded by the human dnc homologs and by dnc, cDNAs f rom three of the rat loci (PDE2, PDE3 and PDE4) had a structure consis tent with alternative splicing of the 5' coding regions of their respe ctive mRNAs. UCR1, and in one case a portion of UCR2, were absent in o ne of the alternatively spliced transcripts from these three loci. RNa se protection analysis showed that the rat PDE3 and PDE4 loci were eac h expressed at relatively constant levels in multiple regions of the b rain, while PDEZ transcripts were more abundant in temporal cortex and brainstem. One of the alternatively spliced mRNAs from the PDE4 locus was relatively more abundant in temporal cortex and cerebellum. One a lternatively spliced transcript from the PDE3 locus was expressed more abundantly in parietal cortex. Both of the alternatively spliced tran scripts from the human DPDE4 locus (the homolog of rat PDE4) were expr essed in temporal cortex.