Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Sci Rep. 2024 Nov 30;14(1):29760. doi: 10.1038/s41598-024-80276-7.
GALNT2, also known as polypeptide N-acetylgalactosaminyltransferase 2, is an enzyme that catalyzes the initial step of O-linked glycosylation, a crucial posttranslational modification that affects protein folding, stability, and function. Alterations in GALNT2 activity have been implicated in various diseases, such as cancer, metabolic disorders, and cardiovascular diseases, highlighting its importance in maintaining normal physiological functions. To investigate the impact of GalNT2 overexpression in vivo for the first time, we generated a conditional transgenic mouse line in which GalNT2 was expressed specifically in the pancreas. Heterozygous overexpression leads to a loss of acinar mass and pancreatic steatosis, whereas homozygous overexpression causes complete pancreatic loss and results in a lethal phenotype. Using a reporter gene mouse line, we demonstrated that adipocytes originate through transdifferentiation from pancreatic cells. GalNT2 overexpression results in additional O-glycosylation sites, which we analyzed through PNA lectin enrichment and mass spectrometric proteome analysis.
GALNT2，也被称为多肽 N-乙酰半乳糖胺转移酶 2，是一种酶，能够催化 O-糖基化的初始步骤，这是一种关键的翻译后修饰，影响蛋白质的折叠、稳定性和功能。GALNT2 活性的改变与各种疾病有关，如癌症、代谢紊乱和心血管疾病，突出了其在维持正常生理功能中的重要性。为了首次在体内研究 GalNT2 的过表达，我们生成了一种条件性转基因小鼠系，其中 GalNT2 特异性表达在胰腺中。杂合子过表达导致腺泡质量的丧失和胰腺脂肪变性，而纯合子过表达导致胰腺完全丧失，并导致致命表型。使用报告基因小鼠系，我们证明脂肪细胞是通过胰腺细胞的转分化而来的。GalNT2 的过表达导致额外的 O-糖基化位点，我们通过 PNA 凝集素富集和质谱蛋白质组学分析进行了分析。
