Dataset Information

Biomarkers of favorable immune capacity in growth hormone receptor knockout pig model

ABSTRACT: Laron Syndrome (LS) is a rare hereditary disease in humans caused by a mutation in the growth hormone receptor gene which leads to high levels of circulating GH [1]. The disease is characterized by short statue, obesity, transient hypoglycemia during youth and low incidences of cancer and diabetes [2]. Thus making it interesting to study the underlying mechanisms. Recently a porcine model to mimic human LS was developed [3]. Growth hormone receptors are expressed on various cells of the immune system yet the extent to which dysregulation of GH might affect immune function in LS is poorly understood [4]. Therefore we decided to characterize the influence of growth hormone receptor knockout on the immune function of these animals by analyzing the proteome of their CD4+ and CD4- peripheral blood mononuclear cells (PBMC). 1. Werner, H.; Sarfstein, R.; et al. Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation. Cells 2020, 9, doi:10.3390/cells9112446. 2. Werner, H.; Lapkina-Gendler, L.; et al. Genome-Wide Profiling of Laron Syndrome Patients Identifies Novel Cancer Protection Pathways. Cells 2019, 8, doi:10.3390/cells8060596. 3. Hinrichs, A.; Kessler, B.; et al. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver. Mol Metab 2018, 11, 113-128, doi:10.1016/j.molmet.2018.03.006. 4. Hattori, N. Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system. Growth Horm IGF Res 2009, 19, 187-197, doi:10.1016/j.ghir.2008.12.001.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Blood Cell, Blood

SUBMITTER: Roxane Degroote

LAB HEAD: Stefanie M Hauck

PROVIDER: PXD038772 | Pride | 2023-07-20

REPOSITORIES: Pride

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Publications

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

Schilloks Marie-Christin MC Giese Isabella-Maria IM Hinrichs Arne A Korbonits Lucia L Hauck Stefanie M SM Wolf Eckhard E Deeg Cornelia A CA

Biomolecules 20230326 4

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 immunometaboli ...[more]

PMID: 37189345

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Project description:This a model from the article: Model-projected mechanistic bases for sex differences in growth hormone regulation in humans. Farhy LS, Bowers CY, Veldhuis JD. Am J Physiol Regul Integr Comp Physiol 2007 Apr;292(4):R1577-93 17185408 , Abstract: Models of physiological systems facilitate rational experimental design, inference, and prediction. A recent construct of regulated growth hormone (GH) secretion interlinks the actions of GH-releasing hormone (GHRH), somatostatin (SRIF), and GH secretagogues (GHS) with GH feedback in the rat (Farhy LS, Veldhuis JD. Am J Physiol Regul Integr Comp Physiol 288: R1649-R1663, 2005). In contrast, no comparable formalism exists to explicate GH dynamics in any other species. The present analyses explore whether a unifying model structure can represent species- and sex-defined distinctions in the human and rodent. The consensus principle that GHRH and GHS synergize in vivo but not in vitro was explicable by assuming that GHS 1) evokes GHRH release from the brain, 2) opposes inhibition by SRIF both in the hypothalamus and on the pituitary gland, and 3) stimulates pituitary GH release directly and additively with GHRH. The gender-selective principle that GH pulses are larger and more irregular in women than men was conferrable by way of 4) higher GHRH potency and 5) greater GHS efficacy. The overall construct predicts GHRH/GHS synergy in the human only in the presence of SRIF when the brain-pituitary nexus is intact, larger and more irregular GH pulses in women, and observed gender differences in feedback by GH and the single and paired actions of GHRH, GHS, and SRIF. The proposed model platform should enhance the framing and interpretation of novel clinical hypotheses and create a basis for interspecies generalization of GH-axis regulation. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Farhy LS, Bowers CY, Veldhuis JD. (2007) - version03 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Dataset Information

Biomarkers of favorable immune capacity in growth hormone receptor knockout pig model

Publications

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

Similar Datasets

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