Cargando…
Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR)
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 dyspla...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759348/ https://www.ncbi.nlm.nih.gov/pubmed/23720234 http://dx.doi.org/10.1242/dmm.011965 |
_version_ | 1782477245347004416 |
---|---|
author | Sheehan-Rooney, Kelly Swartz, Mary E. Zhao, Feng Liu, Dong Eberhart, Johann K. |
author_facet | Sheehan-Rooney, Kelly Swartz, Mary E. Zhao, Feng Liu, Dong Eberhart, Johann K. |
author_sort | Sheehan-Rooney, Kelly |
collection | PubMed |
description | 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 quick 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. |
format | Online Article Text |
id | pubmed-3759348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-37593482013-09-16 Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) Sheehan-Rooney, Kelly Swartz, Mary E. Zhao, Feng Liu, Dong Eberhart, Johann K. Dis Model Mech Research Report 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 quick 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. The Company of Biologists Limited 2013-09 2013-05-29 /pmc/articles/PMC3759348/ /pubmed/23720234 http://dx.doi.org/10.1242/dmm.011965 Text en © 2013. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Report Sheehan-Rooney, Kelly Swartz, Mary E. Zhao, Feng Liu, Dong Eberhart, Johann K. Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) |
title | Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) |
title_full | Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) |
title_fullStr | Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) |
title_full_unstemmed | Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) |
title_short | Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) |
title_sort | ahsa1 and hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (hdr) |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759348/ https://www.ncbi.nlm.nih.gov/pubmed/23720234 http://dx.doi.org/10.1242/dmm.011965 |
work_keys_str_mv | AT sheehanrooneykelly ahsa1andhsp90activityconfersmoreseverecraniofacialphenotypesinazebrafishmodelofhypoparathyroidismsensorineuraldeafnessandrenaldysplasiahdr AT swartzmarye ahsa1andhsp90activityconfersmoreseverecraniofacialphenotypesinazebrafishmodelofhypoparathyroidismsensorineuraldeafnessandrenaldysplasiahdr AT zhaofeng ahsa1andhsp90activityconfersmoreseverecraniofacialphenotypesinazebrafishmodelofhypoparathyroidismsensorineuraldeafnessandrenaldysplasiahdr AT liudong ahsa1andhsp90activityconfersmoreseverecraniofacialphenotypesinazebrafishmodelofhypoparathyroidismsensorineuraldeafnessandrenaldysplasiahdr AT eberhartjohannk ahsa1andhsp90activityconfersmoreseverecraniofacialphenotypesinazebrafishmodelofhypoparathyroidismsensorineuraldeafnessandrenaldysplasiahdr |