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Ikaros-Associated Diseases: From Mice to Humans and Back Again
The normal expression of Ikaros (IKZF1) is important for the proper functioning of both the human and murine immune systems. Whilst our understanding of IKZF1 in the immune system has been greatly enhanced by the study of mice carrying mutations in Ikzf1, analyses of human patients carrying germline...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330404/ https://www.ncbi.nlm.nih.gov/pubmed/34354970 http://dx.doi.org/10.3389/fped.2021.705497 |
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author | Boast, Brigette Nunes-Santos, Cristiane de Jesus Kuehn, Hye Sun Rosenzweig, Sergio D. |
author_facet | Boast, Brigette Nunes-Santos, Cristiane de Jesus Kuehn, Hye Sun Rosenzweig, Sergio D. |
author_sort | Boast, Brigette |
collection | PubMed |
description | The normal expression of Ikaros (IKZF1) is important for the proper functioning of both the human and murine immune systems. Whilst our understanding of IKZF1 in the immune system has been greatly enhanced by the study of mice carrying mutations in Ikzf1, analyses of human patients carrying germline IKZF1 mutations have been instrumental in understanding its biological role within the human immune system and its effect on human disease. A myriad of different mutations in IKZF1 have been identified, spanning across the entire gene causing differential clinical outcomes in patients including immunodeficiency, immune dysregulation, and cancer. The majority of mutations in humans leading to IKAROS-associated diseases are single amino acid heterozygous substitutions that affect the overall function of the protein. The majority of mutations studied in mice however, affect the expression of the protein rather than its function. Murine studies would suggest that the complete absence of IKZF1 expression leads to severe and sometimes catastrophic outcomes, yet these extreme phenotypes are not commonly observed in patients carrying IKZF1 heterozygous mutations. It is unknown whether this discrepancy is simply due to differences in zygosity, the role and regulation of IKZF1 in the murine and human immune systems, or simply due to a lack of similar controls across both groups. This review will focus its analysis on the current literature surrounding what is known about germline IKZF1 defects in both the human and the murine immune systems, and whether existing mice models are indeed accurate tools to study the effects of IKZF1-associated diseases. |
format | Online Article Text |
id | pubmed-8330404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83304042021-08-04 Ikaros-Associated Diseases: From Mice to Humans and Back Again Boast, Brigette Nunes-Santos, Cristiane de Jesus Kuehn, Hye Sun Rosenzweig, Sergio D. Front Pediatr Pediatrics The normal expression of Ikaros (IKZF1) is important for the proper functioning of both the human and murine immune systems. Whilst our understanding of IKZF1 in the immune system has been greatly enhanced by the study of mice carrying mutations in Ikzf1, analyses of human patients carrying germline IKZF1 mutations have been instrumental in understanding its biological role within the human immune system and its effect on human disease. A myriad of different mutations in IKZF1 have been identified, spanning across the entire gene causing differential clinical outcomes in patients including immunodeficiency, immune dysregulation, and cancer. The majority of mutations in humans leading to IKAROS-associated diseases are single amino acid heterozygous substitutions that affect the overall function of the protein. The majority of mutations studied in mice however, affect the expression of the protein rather than its function. Murine studies would suggest that the complete absence of IKZF1 expression leads to severe and sometimes catastrophic outcomes, yet these extreme phenotypes are not commonly observed in patients carrying IKZF1 heterozygous mutations. It is unknown whether this discrepancy is simply due to differences in zygosity, the role and regulation of IKZF1 in the murine and human immune systems, or simply due to a lack of similar controls across both groups. This review will focus its analysis on the current literature surrounding what is known about germline IKZF1 defects in both the human and the murine immune systems, and whether existing mice models are indeed accurate tools to study the effects of IKZF1-associated diseases. Frontiers Media S.A. 2021-07-16 /pmc/articles/PMC8330404/ /pubmed/34354970 http://dx.doi.org/10.3389/fped.2021.705497 Text en Copyright © 2021 Boast, Nunes-Santos, Kuehn and Rosenzweig. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Boast, Brigette Nunes-Santos, Cristiane de Jesus Kuehn, Hye Sun Rosenzweig, Sergio D. Ikaros-Associated Diseases: From Mice to Humans and Back Again |
title | Ikaros-Associated Diseases: From Mice to Humans and Back Again |
title_full | Ikaros-Associated Diseases: From Mice to Humans and Back Again |
title_fullStr | Ikaros-Associated Diseases: From Mice to Humans and Back Again |
title_full_unstemmed | Ikaros-Associated Diseases: From Mice to Humans and Back Again |
title_short | Ikaros-Associated Diseases: From Mice to Humans and Back Again |
title_sort | ikaros-associated diseases: from mice to humans and back again |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330404/ https://www.ncbi.nlm.nih.gov/pubmed/34354970 http://dx.doi.org/10.3389/fped.2021.705497 |
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