ZFIN ID: ZDB-PUB-130708-31
Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR)
Sheehan-Rooney, K., Swartz, M.E., Zhao, F., Liu, D., and Eberhart, J.K.
Date: 2013
Source: Disease models & mechanisms   6(5): 1285-91 (Journal)
Registered Authors: Eberhart, Johann, Liu, Dong, Sheehan-Rooney, Kelly, Swartz, Mary
Keywords: none
MeSH Terms:
  • Animals
  • Craniofacial Abnormalities/metabolism*
  • Craniofacial Abnormalities/pathology*
  • Disease Models, Animal
  • GATA3 Transcription Factor/genetics
  • GATA3 Transcription Factor/metabolism
  • HSP90 Heat-Shock Proteins/antagonists & inhibitors
  • HSP90 Heat-Shock Proteins/metabolism*
  • Hearing Loss, Sensorineural/metabolism*
  • Hearing Loss, Sensorineural/pathology*
  • Humans
  • Hypoparathyroidism/metabolism*
  • Hypoparathyroidism/pathology*
  • Injections
  • Molecular Chaperones/antagonists & inhibitors
  • Molecular Chaperones/metabolism*
  • Morpholinos/administration & dosage
  • Morpholinos/pharmacology
  • Mutation/genetics
  • Nephrosis/metabolism*
  • Nephrosis/pathology*
  • Phenotype
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 23720234 Full text @ Dis. Model. Mech.

The severity of most human birth defects is highly variable. Our ability to diagnose, treat and prevent defects relies on our understanding of this variability. Mutation of the transcription factor GATA3 in humans causes the highly variable hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome. Although named for a triad of defects, individuals with HDR can also exhibit craniofacial defects. Through a forward genetic screen for craniofacial mutants, we isolated a zebrafish mutant in which the first cysteine of the second zinc finger of Gata3 is mutated. Because mutation of the homologous cysteine causes HDR in humans, these zebrafish mutants could be a rapidly available and effective animal model for understanding the role of gata3 in the HDR disease spectrum. We demonstrate that, unexpectedly, the chaperone proteins Ahsa1 and Hsp90 promote severe craniofacial phenotypes in our zebrafish model of HDR syndrome. The strengths of the zebrafish system, including rapid development, genetic tractability and live imaging, make this an important model for variability.