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Schilloks, M.C.* ; Giese, I.M.* ; Hinrichs, A.* ; Korbonits, L.* ; Hauck, S.M. ; Wolf, E.* ; Deeg, C.A.*

Effects of GHR deficiency and juvenile hypoglycemia on immune cells of a porcine model for Laron syndrome.

Biomolecules 13:24 (2023)

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	Open Access Gold

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Ghr-ko ; Laron Syndrome ; Pbmcs ; Hypoglycemia ; Immune Function ; Interferon-α ; Porcine Model ; Proteomics; Growth-hormone Gh; Blood Mononuclear-cells; Coa Dehydrogenase-deficiency; Receptor Gene; T-cells; Lymphocyte Subsets; Cross-linking; Activation; Alpha; Proliferation

ISSN (print) / ISBN 2218-273X

e-ISSN 2218-273X

Journal Biomolecules

Quellenangaben Volume: 13, Issue: 4, Article Number: 24

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)