PUBLICATION

Congenital asplenia due to a tlx1 mutation reduces resistance to Aeromonas hydrophila infection in zebrafish

Authors
Xie, L., Tao, Y., Wu, R., Ye, Q., Xu, H., Li, Y.
ID
ZDB-PUB-191106-10
Date
2019
Source
Fish & shellfish immunology   95: 538-545 (Journal)
Registered Authors
Li, Yun, Tao, Yixi, Xie, Lang, Xu, Hao
Keywords
Aeromonas hydrophila, Congenital asplenia, Disease resistance, tlx1 knock-out
MeSH Terms
  • Aeromonas hydrophila/immunology
  • Aeromonas hydrophila/pathogenicity
  • Animals
  • Disease Resistance/genetics*
  • Fish Diseases/genetics*
  • Fish Diseases/microbiology
  • Gram-Negative Bacterial Infections/immunology
  • Gram-Negative Bacterial Infections/veterinary*
  • Homeodomain Proteins/genetics*
  • Immunity, Innate
  • Mutation
  • Primary Immunodeficiency Diseases/genetics
  • Primary Immunodeficiency Diseases/veterinary*
  • Spleen/abnormalities*
  • Spleen/microbiology
  • Spleen/physiopathology
  • Zebrafish/genetics*
  • Zebrafish/immunology
  • Zebrafish/microbiology
  • Zebrafish Proteins/genetics*
PubMed
31678534 Full text @ Fish Shellfish Immunol.
Abstract
It is documented that tlx1, an orphan homeobox gene, plays critical roles in the regulation of early spleen developmental in mammalian species. However, there is no direct evidence supporting the functions of tlx1 in non-mammalian species, especially in fish. In this study, we demonstrated that tlx1 is expressed in the splenic primordia as early as 52 h post-fertilization (hpf) in zebrafish. A tlx1-/- homozygous mutant line was generated via CRISPR/Cas9 to elucidate the roles of tlx1 in spleen development in zebrafish. In the tlx1-/- background, tlx1-/- cells persisted in the splenic primordia until 52 hpf but were no longer detectable after 53 hpf, suggesting perturbation of early spleen development. The zebrafish also exhibited congenital asplenia caused by the tlx1 mutation. Asplenic zebrafish can survive and breed normally under standard laboratory conditions, but the survival rate of animals infected with Aeromonas hydrophila was significantly lower than that of wild-type (WT) zebrafish. In asplenic zebrafish, the mononuclear phagocyte system was partially impaired, as demonstrated by retarded b7r expression and reduced ccr2 expression after injection with an inactivated A. hydrophila vaccine. Furthermore, the expression of MHCII/IgM was significantly reduced in the congenitally asplenic fish compared with that of the WT zebrafish. Taken together, our data suggest that tlx1 is a crucial regulator of spleen development in fish, as it is in mammals. We have also provided a new perspective for studying the role of the spleen during pathogen challenge in fish.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping