Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo
J. Clin. Invest. Bernd Baumann, et al. 117:1502 doi:10.1172/JCI30876 [Go to this article.]

Figure 1
Mouse model for conditional regulation of IKK activity in pancreatic acinar cells. (A) Transgenic approach for Dox-regulated expression of IKK2-CA and IKK2-DN in the exocrine pancreas. The Ela promoter (Ela.P) controls the expression of rtTA. In the presence of Dox the rtTA protein binds to the bidirectional promoter (tetO)₇ and activates the transcription (arrowheads) of luciferase and either IKK2-DN or IKK2-CA. rTetR, reverse tetracycline repressor; VP16, herpes simplex protein. (B) Luciferase activity was measured in pancreas (Pa), spleen (Sp), and lung (Lu) of double-transgenic Ela.rtTA×IKK2-DN mice without Dox or 24 hours after Dox application i.p. Results were expressed as relative light units (RLU) per μg protein. (C) In vivo imaging of luciferase activity in double-transgenic Ela.rtTA×IKK2-DN mice (Ela.DN 2×Tg) showing restricted luciferase expression to the pancreatic region 24 hours after Dox application. (D) IKK2-DN transgene expression was monitored by immunoblot in pancreatic extracts of Ela.rtTA×IKK2-DN mice 24 and 48 hours after Dox application or in uninduced Ela.rtTA×IKK2-DN controls. ERK2 served as loading control. (E) IKK2 kinase assay (KA) with isolated acini from Dox-treated Ela.rtTA×IKK2-DN mice and single-transgenic IKK2-DN control mice (DN 1×Tg) treated in vitro with cerulein (2 hours) showed decreased IKK activity in Ela.rtTA×IKK2-DN compared with single-transgenic IKK2-DN mice. GST, glutathione-S-transferase.