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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2969-2972.
Prepublished online as a Blood First Edition Paper on July 17, 2008; DOI 10.1182/blood-2008-03-145011.


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PHAGOCYTES

Brief Report

Carboxypeptidase A5 identifies a novel mast cell lineage in the zebrafish providing new insight into mast cell fate determination

J. Tristan Dobson1,2, Jake Seibert1, Evelyn M. Teh1,2, Sahar Da'as1, Robert B. Fraser1,3, Barry H. Paw4,5, Tong-Jun Lin1,2,6, and Jason N. Berman1,2,6

1 IWK Health Centre, and Departments of2 Microbiology and Immunology, and 3 Pathology, Dalhousie University, Halifax, NS; 4 Division of Hematology, Brigham and Women's Hospital and 5 Division of Hematology-Oncology, Children's Hospital Boston, Harvard Medical School, Boston, MA; and 6 Department of Pediatrics, Dalhousie University, Halifax, NS

Mast cells (MCs) play critical roles in allergy and inflammation, yet their development remains controversial due to limitations posed by traditional animal models. The zebrafish provides a highly efficient system for studying vertebrate hematopoiesis. We have identified zebrafish MCs in the gill and intestine, which resemble their mammalian counterparts both structurally and functionally. Carboxypeptidase A5 (cpa5), a MC-specific enzyme, is expressed in zebrafish blood cells beginning at 24 hours post fertilization (hpf). At 28 hpf, colocalization is observed with pu.1, mpo, l-plastin, and lysozyme C, but not fms or cepb{alpha}, identifying these early MCs as a distinct myeloid population arising from a common granulocyte/monocyte progenitor. Morpholino "knock-down" studies demonstrate that transcription factors gata-2 and pu.1, but not gata-1 or fog-1, are necessary for early MC development. These studies validate the zebrafish as an in vivo tool for studying MC ontogeny and function with future capacity for modeling human MC diseases.


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