Initial characterization of myeloid defective mutant myd^310-/-

Abstract

Myeloid cells, mainly including macrophages and neutrophils, are key regulators of the innate immunity in which process they function to phagocytosing pathogens after infection and/or apoptotic cells/unwanted tissues during organogenesis/embryogenesis. However, as suggested by more and more recent researches, myeloid cells like macrophages do more than just this as they also function in homeostasis maintainance, tissue remodeling/regeneration as well as stimulation of the adaptive immune system. Malformation and/or dysregulation of myeloid cells is highly associated with many common diseases, such as acute myeloid leukemia (AML), myelo-dysplastic syndrome, atherosclerosis, arthritis et al. Despite of such importance, the molecular mechanism governing the specification of each myeloid lineage, their subsequent maturation as well as function conferment is still poorly elucidated. To probe this issue, we took advantage of the genetic tractable zebrafish and performed forward genetic analysis. By using neutral red as the scoring marker in an ENU-based three-generation screening, we identified myeloid defective mutant myd³¹⁰, with the loss of macrophages in the brain region. Initial characterization of this mutant revealed the decrease of macrophage lineage on the surface, which presumably resulted from enhanced cell death in this region. Further analysis found distribution pattern change of the neutrophil lineage, which was proposed to be the consequence of immune response via lineage expansion and/or over-activation. Studying mutant like this will provide novel insight into the mechanisms regulating the formation, diversification and function of myeloid cells.

Date of Award	2012
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology