title: Visualizing the dynamics of p21(Waf1/Cip1) cyclin-dependent kinase inhibitor expression in living animals.
abstract: Although the role of p21(Waf1/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 p21(Waf1/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 p21(Waf1/Cip1) gene promoter. In conjunction with a noninvasive bioluminescent imaging technique, p21-p-luc mice enabled us to monitor the endogenous p21(Waf1/Cip1) gene expression in vivo. By monitoring and quantifying the p21(Waf1/Cip1) gene expression repeatedly in the same mouse throughout its entire lifespan, we were able to unveil the dynamics of p21(Waf1/Cip1) gene expression in the aging process. We also applied this system to chemically induced skin carcinogenesis and found that the levels of p21(Waf1/Cip1) gene expression rise dramatically in benign skin papillomas, suggesting that p21(Waf1/Cip1) plays a preventative role(s) in skin tumor formation. Surprisingly, moreover, we found that the level of p21(Waf1/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.
authors.affiliation: Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan. ohtani@genome.tokushima-u.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Ohtani
authors.forename: Yuko
authors.initials: Y
authors.lastname: Imamura
authors.forename: Kimi
authors.initials: K
authors.lastname: Yamakoshi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirota
authors.forename: Rika
authors.initials: R
authors.lastname: Nakayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubo
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.forename: Akiko
authors.initials: A
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirao
authors.forename: Takatsune
authors.initials: T
authors.lastname: Shimizu
authors.forename: David J
authors.initials: DJ
authors.lastname: Mann
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Arase
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Nakao
authors.initials: N
authors.lastname: Kazuki
authors.forename: Eiji
authors.initials: E
authors.lastname: Hara
mesh_terms: D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D049454:Firefly Luciferin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049408:Luminescent Agents / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D049408:Luminescent Agents; D049454:Firefly Luciferin; D008156:Luciferases