Krakowski M, Yeung B, Abdelmalik R, Good A, Mocnik L, Sosa-Pineda B, St-Onge L, Gruss P, Sarvetnick N
The Scripps Research Institute, Department of Immunology, La Jolla, California 92037, USA.
Pancreas. 2000 Nov;21(4):399-406. doi: 10.1097/00006676-200011000-00011.
In the presence of interferon-gamma (IFN-gamma), pancreatic ductal epithelial cells grow continuously, and islets undergo neogenesis. To determine whether these new islets are derived from conventional precursors, we tested whether IFN-gamma can complement the loss of transcription factors known to regulate pancreatic development. We analyzed the effect of a transgene on lethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by intercrossing such mice with transgenic mice whose pancreatic cells make IFN-gamma (ins-IFN-gamma mice). However, IFN-gamma expression did not rescue these mice from the lethal mutations, because no homozygous knockout mice carrying the IFN-gamma transgene survived, despite the survival of all other hemizygous gene combinations. This outcome demonstrates that the pathway for IFN-gamma regeneration requires the participation of Pax4, Pax6, and Pdx-1. We conclude that the striking islet regeneration observed in the ins-IFN-gamma NOD strain is regulated by the same transcription factors that control initial pancreatic development.
在存在干扰素-γ（IFN-γ）的情况下，胰腺导管上皮细胞持续生长，胰岛发生新生。为了确定这些新胰岛是否源自传统前体，我们测试了IFN-γ是否能够弥补已知调控胰腺发育的转录因子的缺失。我们通过将缺乏转录因子Pax4、Pax6或Pdx-1的小鼠与胰腺细胞产生IFN-γ的转基因小鼠（ins-IFN-γ小鼠）杂交，分析了转基因对这些小鼠致死性的影响。然而，IFN-γ的表达并未使这些小鼠从致死性突变中获救，因为尽管所有其他半合子基因组合的小鼠存活了下来，但没有携带IFN-γ转基因的纯合敲除小鼠存活。这一结果表明，IFN-γ再生途径需要Pax4、Pax6和Pdx-1的参与。我们得出结论，在ins-IFN-γ NOD品系中观察到的显著胰岛再生受控制初始胰腺发育的相同转录因子调控。
