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Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome

Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the...

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Autores principales: Schilloks, Marie-Christin, Giese, Isabella-Maria, Hinrichs, Arne, Korbonits, Lucia, Hauck, Stefanie M., Wolf, Eckhard, Deeg, Cornelia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135491/
https://www.ncbi.nlm.nih.gov/pubmed/37189345
http://dx.doi.org/10.3390/biom13040597
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author Schilloks, Marie-Christin
Giese, Isabella-Maria
Hinrichs, Arne
Korbonits, Lucia
Hauck, Stefanie M.
Wolf, Eckhard
Deeg, Cornelia A.
author_facet Schilloks, Marie-Christin
Giese, Isabella-Maria
Hinrichs, Arne
Korbonits, Lucia
Hauck, Stefanie M.
Wolf, Eckhard
Deeg, Cornelia A.
author_sort Schilloks, Marie-Christin
collection PubMed
description Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the same features as humans with LS-like transient juvenile hypoglycemia. This study aimed to investigate the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. GHR are located on various cell types of the immune system. Therefore, we investigated lymphocyte subsets, proliferative and respiratory capacity of peripheral blood mononuclear cells (PBMCs), proteome profiles of CD4(−) and CD4(+) lymphocytes and IFN-α serum levels between wild-type (WT) controls and GHR-KO pigs, which revealed significant differences in the relative proportion of the CD4(+)CD8α(−) subpopulation and in IFN-α levels. We detected no significant difference in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. But proteome analysis of CD4(+) and CD4(−) lymphocyte populations revealed multiple significant protein abundance differences between GHR-KO and WT pigs, involving pathways related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation. This study highlights the potential use of GHR-KO pigs as a model for studying the effects of impaired GHR signaling on immune functions.
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spelling pubmed-101354912023-04-28 Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome Schilloks, Marie-Christin Giese, Isabella-Maria Hinrichs, Arne Korbonits, Lucia Hauck, Stefanie M. Wolf, Eckhard Deeg, Cornelia A. Biomolecules Article Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the same features as humans with LS-like transient juvenile hypoglycemia. This study aimed to investigate the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. GHR are located on various cell types of the immune system. Therefore, we investigated lymphocyte subsets, proliferative and respiratory capacity of peripheral blood mononuclear cells (PBMCs), proteome profiles of CD4(−) and CD4(+) lymphocytes and IFN-α serum levels between wild-type (WT) controls and GHR-KO pigs, which revealed significant differences in the relative proportion of the CD4(+)CD8α(−) subpopulation and in IFN-α levels. We detected no significant difference in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. But proteome analysis of CD4(+) and CD4(−) lymphocyte populations revealed multiple significant protein abundance differences between GHR-KO and WT pigs, involving pathways related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation. This study highlights the potential use of GHR-KO pigs as a model for studying the effects of impaired GHR signaling on immune functions. MDPI 2023-03-26 /pmc/articles/PMC10135491/ /pubmed/37189345 http://dx.doi.org/10.3390/biom13040597 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schilloks, Marie-Christin
Giese, Isabella-Maria
Hinrichs, Arne
Korbonits, Lucia
Hauck, Stefanie M.
Wolf, Eckhard
Deeg, Cornelia A.
Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome
title Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome
title_full Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome
title_fullStr Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome
title_full_unstemmed Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome
title_short Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome
title_sort effects of ghr deficiency and juvenile hypoglycemia on immune cells of a porcine model for laron syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135491/
https://www.ncbi.nlm.nih.gov/pubmed/37189345
http://dx.doi.org/10.3390/biom13040597
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