M. Krakowski et al., IFN-gamma overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death, PANCREAS, 21(4), 2000, pp. 399-406
In the presence of interferon-gamma (IFN-gamma), pancreatic ductal epitheli
al cells grow continuously, and islets undergo neogenesis. To determine whe
ther these new islets are derived from conventional precursors, we tested w
hether IFN-gamma can complement the loss of transcription factors known to
regulate pancreatic development. We analyzed the effect of a transgene on l
ethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by
intercrossing such mice with transgenic mice whose pancreatic cells make I
FN-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 othe
r hemizygous gene combinations. This outcome demonstrates that the pathway
for IFN-gamma regeneration requires the participation of Pax4, Pax6, and Pd
x-1. We conclude that the striking islet regeneration observed in the ins-I
FN-gamma NOD strain is regulated by the same transcription factors that con
trol initial pancreatic development.