Walters Kevin B, Dodd M Ernest, Mathias Jonathan R, Gallagher Andrea J, Bennin David A, Rhodes Jennifer, Kanki John P, Look A Thomas, Grinblat Yevgenya, Huttenlocher Anna
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Dev Dyn. 2009 Jan;238(1):86-99. doi: 10.1002/dvdy.21821.
Factor for adipocyte differentiation 24 (fad24) is a novel gene that has been implicated in adipocyte differentiation and DNA replication. In a screen for zebrafish mutants that have an abnormal tissue distribution of neutrophils, we identified an insertional allele of fad24, fad24hi1019. Homozygous fad24hi1019 larvae exhibit muscle degeneration accompanied by leukocyte infiltration. Muscle degeneration was extensive and included tissue apoptosis and disorganized, poorly striated muscle fibers. Blocking apoptosis using pan-caspase inhibitors resulted in decreased neutrophil recruitment into the body of the larva, suggesting a causative link between apoptosis and leukocyte infiltration. These findings suggest that zebrafish is a powerful genetic model system to address the interplay between muscle degeneration and leukocyte infiltration, and indicate that tissue apoptosis may contribute to neutrophil recruitment in some inflammatory states.
脂肪细胞分化因子24(fad24)是一种与脂肪细胞分化和DNA复制有关的新基因。在筛选中性粒细胞组织分布异常的斑马鱼突变体时,我们鉴定出fad24的一个插入等位基因fad24hi1019。纯合的fad24hi1019幼虫表现出肌肉退化并伴有白细胞浸润。肌肉退化广泛,包括组织凋亡以及肌肉纤维紊乱、横纹不清晰。使用泛半胱天冬酶抑制剂阻断凋亡导致幼虫体内中性粒细胞募集减少,这表明凋亡与白细胞浸润之间存在因果关系。这些发现表明,斑马鱼是研究肌肉退化与白细胞浸润之间相互作用的强大遗传模型系统,并表明组织凋亡可能在某些炎症状态下促进中性粒细胞的募集。