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A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1)
Signal transducer and activator of transcription (STAT) proteins act downstream of cytokine receptors to facilitate changes in gene expression that impact a range of developmental and homeostatic processes. Patients harbouring loss-of-function (LOF) STAT5B mutations exhibit postnatal growth failure...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063521/ https://www.ncbi.nlm.nih.gov/pubmed/36995466 http://dx.doi.org/10.1007/s00018-023-04759-y |
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author | Heidary, Somayyeh Awasthi, Nagendra Page, Nicole Allnutt, Theo Lewis, Rowena S. Liongue, Clifford Ward, Alister C. |
author_facet | Heidary, Somayyeh Awasthi, Nagendra Page, Nicole Allnutt, Theo Lewis, Rowena S. Liongue, Clifford Ward, Alister C. |
author_sort | Heidary, Somayyeh |
collection | PubMed |
description | Signal transducer and activator of transcription (STAT) proteins act downstream of cytokine receptors to facilitate changes in gene expression that impact a range of developmental and homeostatic processes. Patients harbouring loss-of-function (LOF) STAT5B mutations exhibit postnatal growth failure due to lack of responsiveness to growth hormone as well as immune perturbation, a disorder called growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1). This study aimed to generate a zebrafish model of this disease by targeting the stat5.1 gene using CRISPR/Cas9 and characterising the effects on growth and immunity. The zebrafish Stat5.1 mutants were smaller, but exhibited increased adiposity, with concomitant dysregulation of growth and lipid metabolism genes. The mutants also displayed impaired lymphopoiesis with reduced T cells throughout the lifespan, along with broader disruption of the lymphoid compartment in adulthood, including evidence of T cell activation. Collectively, these findings confirm that zebrafish Stat5.1 mutants mimic the clinical impacts of human STAT5B LOF mutations, establishing them as a model of GHISID1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-023-04759-y. |
format | Online Article Text |
id | pubmed-10063521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-100635212023-04-01 A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) Heidary, Somayyeh Awasthi, Nagendra Page, Nicole Allnutt, Theo Lewis, Rowena S. Liongue, Clifford Ward, Alister C. Cell Mol Life Sci Original Article Signal transducer and activator of transcription (STAT) proteins act downstream of cytokine receptors to facilitate changes in gene expression that impact a range of developmental and homeostatic processes. Patients harbouring loss-of-function (LOF) STAT5B mutations exhibit postnatal growth failure due to lack of responsiveness to growth hormone as well as immune perturbation, a disorder called growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1). This study aimed to generate a zebrafish model of this disease by targeting the stat5.1 gene using CRISPR/Cas9 and characterising the effects on growth and immunity. The zebrafish Stat5.1 mutants were smaller, but exhibited increased adiposity, with concomitant dysregulation of growth and lipid metabolism genes. The mutants also displayed impaired lymphopoiesis with reduced T cells throughout the lifespan, along with broader disruption of the lymphoid compartment in adulthood, including evidence of T cell activation. Collectively, these findings confirm that zebrafish Stat5.1 mutants mimic the clinical impacts of human STAT5B LOF mutations, establishing them as a model of GHISID1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-023-04759-y. Springer International Publishing 2023-03-30 2023 /pmc/articles/PMC10063521/ /pubmed/36995466 http://dx.doi.org/10.1007/s00018-023-04759-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Heidary, Somayyeh Awasthi, Nagendra Page, Nicole Allnutt, Theo Lewis, Rowena S. Liongue, Clifford Ward, Alister C. A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) |
title | A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) |
title_full | A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) |
title_fullStr | A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) |
title_full_unstemmed | A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) |
title_short | A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1) |
title_sort | zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (ghisid1) |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063521/ https://www.ncbi.nlm.nih.gov/pubmed/36995466 http://dx.doi.org/10.1007/s00018-023-04759-y |
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