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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1498-1503.
Prepublished online as a Blood First Edition Paper on May 13, 2004; DOI 10.1182/blood-2003-10-3404.
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Submitted October 3, 2003
Accepted March 29, 2004
Erythropoietin gene from a teleost fish, Fugu rubripes
Chih-Fong Chou, Sumanty Tohari, Sydney Brenner, and Byrappa Venkatesh*
Molecular Genetics Lab, Institute of Molecular and Cell Biology, Singapore
* Corresponding author; email: mcbbv{at}imcb.a-star.edu.sg.
In this paper we report the cloning and characterization of erythropoietin (Epo) gene from the pufferfish, Fugu rubripes. This is the first non-mammalian Epo gene to be cloned. The Fugu Epo comprises five exons and four introns similar to the human EPO, and encodes a 185-amino acid protein that is 32% to 34% identical to Epo from various mammals. The synteny of genes at the Epo locus is conserved between the Fugu and humans. Unlike in mammals in which adult kidney is the primary Epo-producing organ, the heart is the main Epo-producing organ in adult Fugu. In addition to the heart, Fugu Epo is also expressed in the liver and brain similar to the human EPO. Interestingly, the transcripts in the Fugu brain are generated from a distal promoter and include an alternatively spliced first coding exon. No such brain-specific alternative splicing of Epo has been reported in mammals so far. Transient transfection studies in a fish hepatoma cell line (PLHC-1) and a human hepatoma cell line (HepG2) suggest that although Fugu Epo promoter many not be hypoxia inducible, the gene may be regulated by hypoxia.

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