Structure and expression of the rat transthyretin (prealbumin) gene

• Published in: The Journal of biological chemistry Vol. 263; no. 1; pp. 480 - 488
• Main Authors: Fung, W P, Thomas, T, Dickson, P W, Aldred, A R, Milland, J, Dziadek, M, Power, B, Hudson, P, Schreiber, G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 05.01.1988; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Base Composition; Base Sequence; Biological and medical sciences; Biotechnology; Choroid Plexus - metabolism; Cloning, Molecular; DNA Restriction Enzymes; Fundamental and applied biological sciences. Psychology; Genes; Genes, Homeobox; Genes. Genome; Genetic engineering; Genetic technics; Hepatectomy; Inflammation; Methods. Procedures. Technologies; Molecular and cellular biology; Molecular cloning; Molecular genetics; Molecular Sequence Data; Prealbumin - genetics; Promoter Regions, Genetic; Rats; Rats, Inbred BUF; RNA, Messenger - genetics; Transcription, Genetic; Turpentine; Brain; Rat; Nucleotide sequence; In situ; Rodentia; Gene organization; Hybridization; Cerebrospinal fluid; Gene expression; Hepatectomy; Autoradiography; Vertebrata; Mammalia; Development; TBPA; Serum; Molecular cloning; Structure; Transcription initiation; Comparative study
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)57418-X

The rat transthyretin gene, 7.3 kilobase pairs (kb) long, with 14.5 kb of 5' flanking and 12.2 kb of 3' flanking region was cloned and characterized. The gene contained four exons. A “TATA box” sequence (5'-TATATAA-3') and a “CAAT box” sequence (5'-GTCAAT-3') were located 23 and 95 nucleotides upstream, respectively, from the major transcription start site. Nucleotides -51 to -189 were highly conserved (93% homology between rats and humans, 97% homology between rats and mice). Tandem repeats of sequences of 5'-AC-3' and 5'-ACACATGC-3' in the 5' flanking region, of 5'-GAAA-3' in the first intron, and of 5'-GT-3' in the third intron of the gene were observed. Using specific cDNA probes, tissue specificity and regulation of transthyretin mRNA biosynthesis during embryogenesis were analyzed. Transthyretin expression occurred first in the yolk sac, then decreased when expression increased in fetal liver. Presumptive choroid plexus cells in the inner lining of the neural tube expressed transthyretin early in gestation (11 days before birth) with a maximum immediately preceding the spurt of brain growth around birth. Partial hepatectomy of adult rats induced both an acute phase response and regenerative growth in liver. The decrease in transcription of the transthyretin gene in liver, which is characteristic for the acute phase response, was overridden by stimulation of gene expression after partial hepatectomy. This stimulation also affected transthyretin expression in choroid plexus.