Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.
Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, D-85764 Oberschleißheim, Germany.
Biomolecules. 2023 Mar 26;13(4):597. doi: 10.3390/biom13040597.
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 (). A -knockout (-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 -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 -KO pigs, which revealed significant differences in the relative proportion of the CD4CD8α 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 -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 -KO pigs as a model for studying the effects of impaired GHR signaling on immune functions.
拉隆综合征（LS）是一种罕见的遗传疾病，其特征是由于生长激素受体基因（）突变导致胰岛素样生长因子 1（IGF1）水平降低和生长激素（GH）水平升高。一种生长激素受体基因敲除（-KO）猪被开发为 LS 的模型，其表现出许多与 LS 样短暂性青少年低血糖相似的特征。本研究旨在研究受损的 GHR 信号对 -KO 猪免疫功能和免疫代谢的影响。GHR 位于免疫系统的各种细胞类型上。因此，我们研究了外周血单核细胞（PBMCs）中的淋巴细胞亚群、增殖和呼吸能力、CD4 和 CD4 淋巴细胞的蛋白质组谱以及 IFN-α 血清水平，结果显示 CD4CD8α 亚群的相对比例和 IFN-α 水平存在显著差异。我们未发现两组间 PBMCs 的呼吸能力和多克隆刺激能力有显著差异。但是 CD4 和 CD4 淋巴细胞群的蛋白质组分析显示，-KO 和 WT 猪之间存在多种显著的蛋白质丰度差异，涉及与氨基酸代谢、脂肪酸的β氧化、胰岛素分泌信号和氧化磷酸化相关的途径。本研究强调了 -KO 猪作为研究受损 GHR 信号对免疫功能影响的模型的潜在用途。
