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- Title
Is c-Jun Critical for Pancreas Development? Loss-of-Function Approach with Pancreas-Specific c-Jun Deficient Mice.
- Authors
Yamamoto, Kaoru; Miyatsuka, Takeshi; Tanaka, Ayako; Kato, Ken; Shiraiwa, Toshihiko; Matsuhisa, Munehide; Yamasaki, Yoshimitsu; Matsuoka, Taka-Aki; Kaneto, Hideaki
- Abstract
It is well known that activating protein-1 (AP-1) is involved in a variety of cellular function such as proliferation, differentiation, apoptosis, and ontogenesis. While AP-1 is a dimmer complex consisting of different subunits, c-Jun is known as one of its major components. Also, it has been shown that mice lacking c-Jun are embryonic lethal and that c-Jun is essential for liver and heart development, but a role of c-Jun in pancreas is not well known. Pancreas has its embryological origin in two buds developing on the dorsal and ventral side of the duodenum. The ventral bud arises immediately adjacent to the hepatic diverticulum, and the dorsal bud arises on the opposite side of the gut tube. The aim of this study was to examine a possible role c-Jun in pancreas. First, c-Jun was strongly expressed in pancreatic duct-like structures at embryonic day15.5, while lower level expression was observed in some population of adult pancreas, implying that c-Jun might play some 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 e-Jun floxed mice. It is noted that Ptf1a is a transcription factor which expression is confined to pancreatic stem/progenitor cells, which give rise to all three types of pancreatic tissue: endocrine, exocrine, and duct. The deletion of c-Jun in Ptf1a-Cre c-Jun flox/flox pancreas was reconfirmed by immunohistochemistry at embryonic day 15.5 and RT-PCR at adult stage. Contrary to our expectation, however, there was no morphological difference in pancreas between Ptf1a-Cre; c-Jun flox/flox mice and control littermates. Also, there was no difference in body weight, pancreas weight, and insulin expression between two groups. Furthermore, to examine whether deletion of c-Jun influences glucose tolerance, we performed intraperitoneal glucose tolerance test, but there was no clear difference in glucose tolerance between Ptf1a-Cre; e-Jun flox/flox and control mice. These results indicate that c-Jun is dispensable for pancreas development at least after Ptf1a promoter is activated.
- Subjects
DIABETES; PANCREAS; CELL proliferation; ONTOGENY; PROTEINS; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA419
- ISSN
0012-1797
- Publication type
Article