Related Experiment Videos
ARNT2 is not required for TCDD developmental toxicity in zebrafish
Amy L Prasch1, Warren Heideman, Richard E Peterson
1Molecular and Environmental Toxicology Center, and School of Pharmacy, University of Wisconsin, 77 Highland Avenue, Madison, WI 53705, USA.
Summary
Zebrafish aryl hydrocarbon receptor 2 (ZfAHR2) mediates dioxin toxicity. However, the zfARNT2 protein is not essential for this developmental toxicity, suggesting other partners for ZfAHR2.
Area of Science:
- Toxicology
- Developmental Biology
- Molecular Biology
Background:
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental toxicity in zebrafish, mediated by the ZfAHR2 receptor.
- The zfARNT2b protein forms a functional heterodimer with ZfAHR2, recognizing XREs and inducing transcription in response to TCDD.
Purpose of the Study:
- To investigate whether zfARNT2 acts as the physiological dimerization partner for ZfAHR2 in mediating TCDD developmental toxicity in zebrafish.
- To test the hypothesis that zfARNT2 is essential for TCDD-induced developmental toxicity.
Main Methods:
- Utilized an antisense morpholino (zfarnt2-MO) to decrease zfARNT2 protein expression.
- Examined TCDD toxicity endpoints in zfARNT2-deficient zebrafish embryos (zfarnt2(-/-)) and compared them to wild-type (WT) embryos.
- Assessed TCDD-induced zfCYP1A expression patterns via immunostaining.
Main Results:
- zfarnt2-MO injection reduced zfARNT2 protein but did not protect against pericardial edema.
- zfarnt2(-/-) embryos showed no protection against TCDD-induced pericardial edema, reduced trunk blood flow, or shortened lower jaw.
- Immunostaining revealed similar TCDD-induced zfCYP1A expression patterns in zfARNT2-deficient and WT embryos.
Conclusions:
- ZfARNT2 is not essential for mediating the developmental toxicity of TCDD in zebrafish.
- Alternate dimerization partner(s) for ZfAHR2 likely exist in vivo to mediate TCDD toxicity.