ZFIN ID: ZDB-PUB-051214-17
Understanding dioxin developmental toxicity using the zebrafish model
Carney, S.A., Prasch, A.L., Heideman, W., and Peterson, R.E.
Date: 2006
Source: Birth defects research. Part A, Clinical and molecular teratology   76(1): 7-18 (Journal)
Registered Authors: Carney, Sara A., Heideman, Warren, Peterson, Richard E., Prasch, Amy
Keywords: TCDD, zebrafish, developmental toxicity, morpholino, AHR, ARNT, CYP1A
MeSH Terms:
  • Animals
  • Aryl Hydrocarbon Hydroxylases/metabolism
  • Cytochrome P-450 CYP1A1/genetics
  • Cytochrome P-450 CYP1A1/metabolism
  • Drug-Related Side Effects and Adverse Reactions
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology
  • Gene Expression Regulation, Developmental/drug effects
  • Larva/drug effects
  • Larva/metabolism
  • Models, Biological*
  • Morpholines/pharmacology
  • Receptors, Aryl Hydrocarbon/antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon/metabolism
  • Teratogens/toxicity*
  • Zebrafish*/embryology
  • Zebrafish*/growth & development
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 16333842 Full text @ Birth Defects Res. Part A Clin. Mol. Teratol.
ABSTRACT
Zebrafish (Danio rerio) have advantages over mammals as an animal model for investigating developmental toxicity. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (dioxin, TCDD), a persistent global contaminant, is the most comprehensively studied developmental toxicant in zebrafish. The hallmark responses of TCDD developmental toxicity manifested in zebrafish larvae include edema, anemia, hemorrhage, and ischemia associated with arrested growth and development. Heart and vasculature development and function are severely impaired, and jaw malformations occur secondary to inhibited chondrogenesis. The swim bladder fails to inflate, and the switch from embryonic to adult erythropoiesis is blocked. This profile of developmental toxicity responses, commonly referred to as "blue sac syndrome" because the edematous yolk sac appears blue, is observed in the larval form of all freshwater fish species exposed to TCDD at the embryonic stage of development. Components of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AHR/ARNT) signaling pathway in zebrafish have been identified and functionally characterized. Their role in mediating TCDD toxicity has been determined using morpholinos to specifically knockdown the translation of zfAHR1, zfAHR2, zfARNT1, and zfARNT2 mRNAs, respectively, and a line of zfARNT2 null mutant zebrafish has provided further insight. These studies have shown that zfAHR2 and zfARNT1 mediate TCDD developmental toxicity. In addition, the growing use of molecular and genomic tools for research on zebrafish have led to advances in our understanding of the mechanism of TCDD developmental toxicity at the molecular level, including the recent finding that toxicity is not mediated by increased cytochrome P4501A (zfCYP1A) expression.
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