TY - JOUR
T1 - Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals
AU - Ohtani, Naoko
AU - Imamura, Yuko
AU - Yamakoshi, Kimi
AU - Hirota, Fumiko
AU - Nakayama, Rika
AU - Kubo, Yoshiaki
AU - Ishimaru, Naozumi
AU - Takahashi, Akiko
AU - Hirao, Atsushi
AU - Shimizu, Takatsune
AU - Mann, David J.
AU - Saya, Hideyuki
AU - Hayashi, Yoshio
AU - Arase, Seiji
AU - Matsumoto, Mitsuru
AU - Nakao, Kazuki
AU - Hara, Eiji
PY - 2007/9/18
Y1 - 2007/9/18
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0706949104
DO - 10.1073/pnas.0706949104
M3 - Article
C2 - 17848507
AN - SCOPUS:35448967856
SN - 0027-8424
VL - 104
SP - 15034
EP - 15039
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 38
ER -