Rat transthyretin (prealbumin). Molecular cloning, nucleotide sequence, and gene expression in liver and brain

Abstract

Transthyretin cDNA was isolated from a rat liver cDNA library. Analysis of the nucleotide sequence revealed a signal peptide-like sequence preceding a section coding for a full length subunit and an untranslated sequence at the 3' end. The deduced primary structure of rat transthyretin was compared with that of human transthyretin. It was highly conserved at the binding sites for thyroxine and the interfaces and core regions of the subunits. The cDNA for transthyretin was used to measure mRNA levels by hybridization. During acute inflammation, the amount of transthyretin mRNA in liver decreased (reaching a minimum of 25% of the normal level 36 h after inducing inflammation), suggesting regulation of transthyretin synthesis at the mRNA level. Transthyretin mRNA was found only in the liver and in the choroid plexus, but not in other parts of the central nervous system nor in the adrenal glands, kidney, spleen, testes, heart, lung, intestine, and ovaries. One gram of choroid plexus contained about 25 times larger amounts of transthyretin mRNA than 1 g of liver. By synthesizing an important hormone carrier protein, the choroid plexus may be an important link in the chemical communication between the central nervous system and the bloodstream.