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\begin_layout Title
Current Studies on Molecular Mechanisms of Iron Homeostasis in Rhinoceroses
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\begin_layout Author
Rose Linzmeier, Ph.D.1
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Department of Pulmonary and Critical Care Medicine and Department of Pathology
 and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095
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and
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 Ryan Thompson2
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Department of Molecular and Experimental Medicine, The Scripps Research
 Institute, La Jolla, CA 92037
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and
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 Sarah LaMere, D.V.M
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and
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 Pauline Lee, Ph.D.
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and
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 Elizabeta Nemeth, Ph.D.
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and
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 Tomas Ganz, M.D., Ph.D.
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and
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 Donald E.
 Paglia, M.D.
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UCLA Hematology Research Laboratory, Department of Pathology and Laboratory
 Medicine, UCLA School of Medicine, Los Angeles, CA 90095
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Look into https://tex.stackexchange.com/q/34746/5654
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\begin_layout Date
2013
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\begin_layout Standard
Iron storage disease (ISD) is a hazardous and clinically underappreciated
 condition commonly acquired by exotic wildlife species when displaced from
 their natural habitats and confined for even short periods under artificial
 conditions.
 An international symposium recently reviewed and validated evidence that
 African black and Sumatran rhinoceroses invariably develop progressive
 ISD commensurate with their times in captivity, whereas African white and
 Indian rhinoceroses do not 
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.
 Since vulnerability to ISD is a species-wide characteristic, it is likely
 to have a genetic basis possibly reflecting evolutionary adaptions to differenc
es in iron bioavailability between browser and grazer diets.
 
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As a biologically essential element that is also highly toxic in excess,
 iron is exquisitely regulated by molecular mechanisms primarily focused
 on interactions between the peptide hepcidin, (the principal iron-regulatory
 hormone), and its receptor ferroportin, (the sole channel for egress of
 intracellular iron into plasma) 
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.
 Iron-regulatory gene sequences from both ISD-susceptible and non-susceptible
 species were compared to search for possible molecular differences.
 DNA was extracted from peripheral blood samples from all four available
 rhinoceros species, and genes encoding hepcidin and ferroportin, as well
 as modulators hemojuvelin, transferrin receptor 2, and HFE protein, were
 cloned and analyzed by PCR amplification.
 Over half of the DNA sequences of these five genes have now been determined
 without identifying any that could account for disparities in iron loading
 among the species.
 Evaluation of the remaining sequences continues, as do studies to determine
 the responsiveness of rhinoceros ferroportin to hepcidin modulation and
 quantitative levels of hepcidin expression 
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.
 
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In addition, liver and spleen mRNA sequences from African black and white
 rhinoceroses were assembled using Trinity RNA-Seq software 
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 and compared with human sequences using the SIFT algorithm 
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.
 Candidate single-nucleotide polymorphisms were independently validated
 by genomic sequencing.
 Mutations were found in four genes that may be associated with primary
 iron disorders or hemolytic anemia in black rhinoceroses: SLC28a2, EPB41,
 MTF1, and STEAP4 
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.
 The functional consequences of these mutations are being determined.
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