title: Tissue-specific deletion of c-Jun in the pancreas has limited effects on pancreas formation.
abstract: It is well known that activating protein-1 (AP-1) is involved in a variety of cellular functions such as proliferation, differentiation, apoptosis, and oncogenesis. AP-1 is a dimer complex consisting of different subunits, and c-Jun is known to be one of its major components. In addition, it has been shown that mice lacking c-Jun are embryonic lethal and that c-Jun is essential for liver and heart development. However, the role of c-Jun in the pancreas is not well known. The aim of this study was to examine the possible role of c-Jun in the pancreas. First, c-Jun was strongly expressed in pancreatic duct-like structures at an embryonic stage, while a lower level of expression was observed in some part of the adult pancreas, implying that c-Jun might play a role during pancreas development. Second, to address this point, we generated pancreas-specific c-Jun knock-out mice (Ptf1a-Cre; c-Jun(flox/flox) mice) by crossing Ptf1a-Cre knock-in mice with c-Jun floxed mice. Ptf1a is a pancreatic transcription factor and its expression is confined to pancreatic stem/progenitor cells, which give rise to all three types of pancreatic tissue: endocrine, exocrine, and duct. Contrary to our expectation, however, there was no morphological difference in the pancreas between Ptf1a-Cre; c-Jun(flox/flox) and control mice. In addition, there was no difference in body weight, pancreas weight, and the expression of various pancreas-related factors (insulin, glucagon, cytokeratin, and amylase) between the two groups. Furthermore, there was no difference in glucose tolerance between Ptf1a-Cre; c-Jun(flox/flox) and control mice. Taken together, although we cannot exclude the possibility that c-Jun ablation is compensated by some unknown factors, c-Jun appears to be dispensable for pancreas development at least after ptf1a gene promoter is activated.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyatsuka
authors.forename: Ayako
authors.initials: A
authors.lastname: Tanaka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Toyoda
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiraiwa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D010179:Pancreas / Q000254:growth & development* / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1