Isolation, characterization, cDNA cloning and gene expression of an avian transthyretin

Russell Grimwade School of Biochemistry, University of Melbourne, Australia.
European Journal of Biochemistry (Impact Factor: 3.58). 09/1991; 200(3):679-87. DOI: 10.1111/j.1432-1033.1991.tb16232.x
Source: PubMed


A chicken liver cDNA library was constructed in bacteriophage lambda gt10. A full-length transthyretin cDNA clone was identified by screening with rat transthyretin cDNA and was sequenced. A three-dimensional model of chicken transthyretin was obtained by computer-graphics-based prediction from the derived amino acid sequence for chicken transthyretin and from the structure of human transthyretin determined by X-ray diffraction analysis [Blake, C.C.F., Geisow, M.J., Oatley, S.J., Rérat, B. & Rérat, C. (1978) J. Mol. Biol. 121, 339-356]. The similarity of the amino acid sequences of chicken and human transthyretins was 75% overall and 100% for the central channel containing the thyroxine-binding site. Also, the organization of the transthyretin gene into exons and introns and the tissue specificity of expression of the transthyretin gene were similar in chicken and mammals, despite an evolutionary distance of about 3 x 10(8) years from their common ancestor, the Cotylosaurus. By far the highest levels of transthyretin mRNA were found in choroid plexus. The data suggest a fundamental role for the cerebral expression of transthyretin in all vertebrates. It has been proposed that this role is the transport of thyroxine from the bloodstream to the brain [Schreiber, G., Aldred, A.R., Jaworowski, A., Nilsson, C., Achen, M.G. & Segal, M.B. (1990) Am. J. Physiol. 258, R338-R345].

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Available from: Samantha J Richardson, Oct 06, 2014
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    • "TTR (also called prealbumin) is one of the transporters of thyroid hormones and cooperates with retinol-binding protein (RBP) and vitamin A (retinol). TTR directly binds the thyroid hormones (T3 and T4) in the central channel constituted by tetrameric assembly of the monomers [29], [30], [31], and it indirectly provides vitamin A as retinol bound to RBP [32]. TTR has a well-established role in regulating spermatogenesis through effects on retinol metabolism in the adult testis of rats. "
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    ABSTRACT: The chicken reproductive system is unique in maintaining its functions including production of eggs or sperm, fertilization of the egg by sperm maintained in sperm nests, production of hormones regulating its growth, development and function, and reproduction. Development of the reproductive organs is a highly regulated process that results in differentiation and proliferation of germ cells in response to predominant regulatory factors such as hormones and transcription factors. However, only a few genes are known to determine morphogenesis of the chicken reproductive tract and their mechanisms are unknown. Therefore, in the present study, we investigated the expression patterns of four genes including SNCA, TOM1L1, TTR and ZEB1 in the gonads at embryonic days 14 and 18, and in immature (12-week-old) and mature (50-week-old) chickens, as well as the reproductive tract including ovary, oviduct and testes of the respective sexes by qRT-PCR, in situ hybridization and immunofluorescence analyses. The expression of SNCA, TOM1L1 and ZEB1 genes was higher in immature and mature female reproductive tracts than expression of TTR. In addition, different temporal and spatial patterns of expression of the four genes were observed during maturation of testis in chickens. Specifically, SNCA, TOM1L1 and TTR were highly expressed in testes of 12-week-old chickens. Moreover, several chicken specific microRNAs (miRs) were demonstrated to affect expression of target gene mRNAs by directly binding to the 3'-UTR of their target genes through actions at the post-transcriptional level as follows: miR-153 and miR-1643 for SNCA; miR-1680* for TTR; and miR-200b and miR-1786 for ZEB1. These results suggest that four-selected genes play an important role in development of the male and female reproductive tract in chickens and expression of most candidate genes is regulated at the post-transcriptional level through specific microRNAs.
    Full-text · Article · Apr 2014 · PLoS ONE
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    • "The deduced amino acid sequence of pig transthyretin was compared with derived amino acid sequences of the transthyretins published earlier for rat (Dickson et al., 1985b; Duan et al., 1989), sheep (Tu et al., 1989), marsupials (Duan et al., 1995), chicken (Duan et al., 1991) and lizard (Achen et al., 1993), and the sequences published by others for human (Mita et al., 1984), mouse (Wakasugi et al., 1985) and rabbit transthyretins (Sundelin et al., 1985) in Fig. 9. The presence of three extra amino acids at its carboxyl-terminal resulted in a total length of 130 amino acids for the pig transthyretin subunit, compared with 127 amino acids for the subunit of other eutherian transthyretins. "
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    ABSTRACT: Thyroxine binding to proteins in pig plasma during electrophoresis was observed in the albumin, but not in the prealbumin and post-albumin regions. Transthyretin could be identified in medium from in vitro pig choroid plexus incubations by size and number of subunits and a very high rate of synthesis and secretion. Its electrophoretic mobility was intermediate between that of thyroxine-binding globulin and albumin. It bound thyroxine, retinol-binding protein, anti-(rat transthyretin) antibodies and behaved similarly to transthyretins from other vertebrate species when plasma was extracted with phenol. Inhibition experiments with the synthetic flavonoid F 21388, analysing the binding of thyroxine, suggested that transthyretin is not a major thyroxine carrier in the bloodstream of pigs. Cloning and sequencing of transthyretin cDNA from both choroid plexus and liver showed that the same transthyretin mRNA is expressed in pig choroid plexus and liver. The amino acid sequence derived from the nucleotide sequence revealed that pig transthyretin differs from the transthyretins of all other studied vertebrate species by an unusual C-terminal extension consisting of the amino acids glycine, alanine and leucine. This extension results from the mutation of a stop codon into a codon for glycine. The unusual C-terminal extensions do not seem to interfere with the access of thyroxine to its binding site in the central channel of transthyretin.
    Full-text · Article · Jun 2008
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    • "The adult rat choroid plexus has 4.4 mg of TTR mRNA per gram wet weight tissue compared with only 0.39 mg of TTR mRNA per gram wet weight liver, that is, an 11‐fold diVerence (Schreiber et al., 1990). In chickens, the adult choroid plexus has 7.2 mg of TTR mRNA per gram wet weight, whereas the liver has only 0.33 mg of TTR mRNA per gram wet weight, that is, a 22‐fold diVerence (Duan et al., 1991). In reptiles, birds, and mammals, TTR is the major protein secreted by the choroid plexus (Harms et al., 1991; Richardson et al., 1994). "
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    ABSTRACT: Advances in four areas of transthyretin (TTR) research result in this being a timely review. Developmental studies have revealed that TTR is synthesized in all classes of vertebrates during development. This leads to a new hypothesis on selection pressure for hepatic TTR synthesis during development only, changing the previous hypotheses from "onset" of hepatic TTR synthesis in adulthood to "maintaining" hepatic TTR synthesis into adulthood. Evolutionary studies have revealed the existence of TTR-like proteins (TLPs) in nonvertebrate species and elucidated some of their functions. Consequently, TTR is an excellent model for the study of the evolution of protein structure, function, and localization. Studies of human diseases have demonstrated that TTR in the cerebrospinal fluid can form amyloid, but more recently there has been recognition of the roles of TTR in depression and Alzheimer's disease. Furthermore, amyloid mutations in human TTR that are the normal residues in other species result in cardiac deposition of TTR amyloid in humans. Finally, a revised model for TTR-thyroxine entry into the cerebrospinal fluid via the choroid plexus, based on data from studies in TTR null mice, is presented. This review concentrates on TTR and its thyroid hormone binding, in development and during evolution, and summarizes what is currently known about TLPs and the role of TTR in diseases affecting the brain.
    Full-text · Article · Feb 2007 · International Review of Cytology
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