Meeting Abstract

P2.64  Thursday, Jan. 5  Exploring the role of hemgn in blood and bone formation using the zebrafish and Antarctic fish models. ALLARD, CA*; GRIM, JG; HU, M; PARKER, SK; POSTLETHWAIT, JH; DETRICH III, HW; Northeastern University; Northeastern University; Northeastern University; Northeastern University; University of Oregon; Northeastern University

The Antarctic marine fauna has been isolated in the cold (-2°C), stable, and oxygen-rich Southern Ocean for 25 million years, and consequently these animals are extremely cold-adapted. One family within the Antarctic notothenioid fishes, the icefish, has lost the capacity to produce erythrocytes and the oxygen transport protein hemoglobin. Their profound anemia makes them an evolutionary mutant model of human anemias. Using a comparative-genomic approach, we have isolated 10 novel genes that are differentially expressed by the red-blooded species Notothenia coriiceps and the “white-blooded” icefish, Chaenocephalus aceratus, and may be novel genes involved in erythropoiesis. We have identified one of these genes (hemogen - hemgn) as a putative ortholog of mammalian EDAG and RP59. In mammals, these genes are involved in the proliferation of blood and bone cells, however, whether the putative ortholog hemgn functions similarly in fishes has not be reported. In the current study, we use a reverse-genetic approach in a zebrafish model system to explore the functions of hemgn in fishes. We show that morpholino knockdown of hemogen mRNA in early zebrafish embryos eliminates erythrocyte production and influences the skeletal phenotype possibly by altering the expression of genes associated with hematopoiesis (e.g., GATA1, SCL, and Globin) and skeletal development (e.g., Col1a1, Col2a1, and ColXa1). These phenotypic changes can be reversed if treated embryos are co-injected with wild type hemogen. Together, these experiments demonstrate that hemogen, like EDAG and RP59 in mammals, plays a role in blood and bone development, and may be a model for future translational studies into the treatment of human anemias.