EXPRESSION OF HIGH-MOLECULAR-WEIGHT TAU IN THE CENTRAL AND PERIPHERALNERVOUS SYSTEMS

Using a novel PCR approach, we have cloned a cDNA encoding the entire high molecular weight tau molecule from rat dorsal root ganglia. The r esulting 2080 bp cDNA differs from low molecular weight rat brain tau by the insertion of a novel 762 bp region (exon 4a) between exons 4 an d 5. This cDNA clone is identical in sequence with a high molecular we ight tau (HMW) cDNA from rat PC12 tumor cells and is closely related t o a HMW tau cDNA from mouse N115 tumor cells. In vitro transcription/t ranslation produces a protein that migrates on SDS-PAGE with the same apparent molecular weight as HMW tau purified from rat sciatic nerve. The HMW tau protein is generated from an 8 kb mRNA, which can be detec ted by northern blots in peripheral ganglia, but not in brain. A more sensitive assay using PCR and Southern blot analysis demonstrates the presence of exon 4a in spinal cord and in retina. In combination with immunohistochemical studies of spinal cord, these data suggest that HM W tau, though primarily in the peripheral nervous system, is also expr essed in limited areas of the central nervous system, although its pre sence cannot be detected in the cerebral cortices.