Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish Fad24.
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.
Walters
Kevin B
KB
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Dodd
M Ernest
ME
Mathias
Jonathan R
JR
Gallagher
Andrea J
AJ
Bennin
David A
DA
Rhodes
Jennifer
J
Kanki
John P
JP
Look
A Thomas
AT
Grinblat
Yevgenya
Y
Huttenlocher
Anna
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007962:Leukocytes / Q000378:metabolism*; D050356:Lipid Metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; C539175:noc3l protein, zebrafish