Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals

Naoko Ohtani, Yuko Imamura, Kimi Yamakoshi, Fumiko Hirota, Rika Nakayama, Yoshiaki Kubo, Naozumi Ishimaru, Akiko Takahashi, Atsushi Hirao, Takatsune Shimizu, David J. Mann, Hideyuki Saya, Yoshio Hayashi, Seiji Arase, Mitsuru Matsumoto, Kazuki Nakao, Eiji Hara

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Although the role of p21Waf1/Cip1 gene expression is well documented in various cell culture studies, its in vivo roles are poorly understood. To gain further insight into the role of p21Waf1/Cip1 gene expression in vivo, we attempted to visualize the dynamics of p21 Waf1/Cip1 gene expression in living animals. In this study, we established a transgenic mice line (p21-p-luc) expressing the firefly luciferase under the control of the p21Waf1/Cip1 gene promoter. In conjunction with a noninvasive bioluminescent imaging technique, p21-p-luc mice enabled us to monitor the endogenous p21Waf1/Cip1 gene expression in vivo. By monitoring and quantifying the p21Waf1/Cip1 gene expression repeatedly in the same mouse throughout its entire lifespan, we were able to unveil the dynamics of p21Waf1/Cip1 gene expression in the aging process. We also applied this system to chemically induced skin carcinogenesis and found that the levels of p21Waf1/Cip1 gene expression rise dramatically in benign skin papillomas, suggesting that p21Waf1/Cip1 plays a preventative role(s) in skin tumor formation. Surprisingly, moreover, we found that the level of p21Waf1/Cip1 expression strikingly increased in the hair bulb and oscillated with a 3-week period correlating with hair follicle cycle progression. Notably, this was accompanied by the expression of p63 but not p53. This approach, together with the analysis of p21 Waf1/Cip1 knockout mice, has uncovered a novel role for the p21 Waf1/Cip1 gene in hair development. These data illustrate the unique utility of bioluminescence imaging in advancing our understanding of the timing and, hence, likely roles of specific gene expression in higher eukaryotes.

Original languageEnglish
Pages (from-to)15034-15039
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number38
DOIs
Publication statusPublished - 2007 Sep 18

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Cyclin-Dependent Kinases
Gene Expression
Hair
Skin
Firefly Luciferases
Hair Follicle
Papilloma
Eukaryota
Knockout Mice
Transgenic Mice
Genes
Carcinogenesis
Cell Culture Techniques

Keywords

  • Aging
  • Cell cycle
  • Hair cycle
  • Imaging

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals. / Ohtani, Naoko; Imamura, Yuko; Yamakoshi, Kimi; Hirota, Fumiko; Nakayama, Rika; Kubo, Yoshiaki; Ishimaru, Naozumi; Takahashi, Akiko; Hirao, Atsushi; Shimizu, Takatsune; Mann, David J.; Saya, Hideyuki; Hayashi, Yoshio; Arase, Seiji; Matsumoto, Mitsuru; Nakao, Kazuki; Hara, Eiji.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 38, 18.09.2007, p. 15034-15039.

Research output: Contribution to journalArticle

Ohtani, N, Imamura, Y, Yamakoshi, K, Hirota, F, Nakayama, R, Kubo, Y, Ishimaru, N, Takahashi, A, Hirao, A, Shimizu, T, Mann, DJ, Saya, H, Hayashi, Y, Arase, S, Matsumoto, M, Nakao, K & Hara, E 2007, 'Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 38, pp. 15034-15039. https://doi.org/10.1073/pnas.0706949104
Ohtani, Naoko ; Imamura, Yuko ; Yamakoshi, Kimi ; Hirota, Fumiko ; Nakayama, Rika ; Kubo, Yoshiaki ; Ishimaru, Naozumi ; Takahashi, Akiko ; Hirao, Atsushi ; Shimizu, Takatsune ; Mann, David J. ; Saya, Hideyuki ; Hayashi, Yoshio ; Arase, Seiji ; Matsumoto, Mitsuru ; Nakao, Kazuki ; Hara, Eiji. / Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 38. pp. 15034-15039.
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