Publications
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Episkopou V, Maeda S, Nishiguchi S, et al., 1993, Disruption of the transthyretin gene results in mice with depressed levels of plasma retinol and thyroid hormone., Proc Natl Acad Sci U S A, Vol: 90, Pages: 2375-2379, ISSN: 0027-8424
Transthyretin (TTR) is thought to play a major role in vitamin A metabolism and thyroid hormone transport in mammals. To investigate the physiological role of the TTR protein in development of the embryo and in the adult, we used gene targeting techniques to generate a null mutation at the mouse ttr locus. The resultant mutant animals are phenotypically normal, viable, and fertile. However, levels of serum retinol, retinol-binding protein, and thyroid hormone are significantly depressed in the mutant animals. These observations demonstrate that the TTR protein maintains normal levels of these metabolites in the circulating plasma.
Soares MB, Turken A, Ishii D, et al., 1986, Rat insulin-like growth factor II gene. A single gene with two promoters expressing a multitranscript family., J Mol Biol, Vol: 192, Pages: 737-752, ISSN: 0022-2836
We have characterized the single-copy rat gene encoding the protein precursor of insulin-like growth factor II (pre-pro-rIGF-II) that is located downstream from and in the same transcriptional orientation as the homologous insulin II gene (5'-insulin-IGF-II-3'). This gene consists of at least three coding exons and utilizes two promoters that generate alternate 5' non-coding exons. Multiple transcripts from both promoters appear primarily in fetal or neonatal tissues (in all of the developmental stages and tissues that we have examined), but they are extremely rare or undetectable in adult tissues, with the exception of the brain and the spinal cord. These transcripts, which exhibit characteristic developmental profiles in various tissues, differ both in the presence of one of the alternate 5' non-coding exons and in the length of their fourth exon. The possible occurrence of differential splicing or differential polyadenylation (or both) in this region is discussed.
Episkopou V, Murphy AJ, Efstratiadis A, 1984, Cell-specified expression of a selectable hybrid gene., Proc Natl Acad Sci U S A, Vol: 81, Pages: 4657-4661, ISSN: 0027-8424
We have inserted into a retroviral vector the structural information encoding the selectable bacterial genes neo and gpt linked, respectively, to the promoters of the herpesvirus thymidine kinase gene and the rat preproinsulin II gene. We have used this recombinant retrovirus construction to transduce insulinoma cell lines that are positive or negative for insulin expression. Selection of the transductants for neo yielded resistant colonies from all of the cell lines, while selection for gpt yielded resistant transductants in relatively high frequency only from insulin-producing cells. The 5' end of the gpt transcripts maps to the authentic preproinsulin capping site of the construction.
Chan SJ, Episkopou V, Zeitlin S, et al., 1984, Guinea pig preproinsulin gene: an evolutionary compromise?, Proc Natl Acad Sci U S A, Vol: 81, Pages: 5046-5050, ISSN: 0027-8424
We characterized a clone carrying the guinea pig preproinsulin gene, which, in contrast to other mammalian preproinsulin genes, is highly divergent in its regions encoding the B and A chains of mature insulin. Blot hybridization analysis indicates that this gene is present in only one copy in the guinea pig genome and that other normal or mutated preproinsulin genes do not exist in this animal. Moreover, the position of introns in this gene and the homology of its 3' flanking region to the corresponding regions of other sequenced mammalian genes show that it has been derived from the common mammalian stock. The rapid evolution of the region encoding the B and A chains can be interpreted, according to our sequence-divergence analysis, as due to the fixation of both neutral and adaptive mutations.
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