Overexpression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells

T Mitsuhashi, Y Aoki, YZ Eksioglu, T Takahashi… - Proceedings of the …, 2001 - pnas.org
T Mitsuhashi, Y Aoki, YZ Eksioglu, T Takahashi, PG Bhide, SA Reeves, VS Caviness Jr
Proceedings of the National Academy of Sciences, 2001pnas.org
We describe a mouse model in which p27Kip1 transgene expression is spatially restricted to
the central nervous system neuroepithelium and temporally controlled with doxycycline.
Transgene-specific transcripts are detectable within 6 h of doxycycline administration, and
maximum nonlethal expression is approached within 12 h. After 18–26 h of transgene
expression, the G1 phase of the cell cycle is estimated to increase from 9 to 13 h in the
neocortical neuroepithelium, the maximum G1 phase length attainable in this proliferative …
We describe a mouse model in which p27Kip1 transgene expression is spatially restricted to the central nervous system neuroepithelium and temporally controlled with doxycycline. Transgene-specific transcripts are detectable within 6 h of doxycycline administration, and maximum nonlethal expression is approached within 12 h. After 18–26 h of transgene expression, the G1 phase of the cell cycle is estimated to increase from 9 to 13 h in the neocortical neuroepithelium, the maximum G1 phase length attainable in this proliferative population in normal mice. Thus our data establish a direct link between p27Kip1 and control of G1 phase length in the mammalian central nervous system and unveil intrinsic mechanisms that constrain the G1 phase length to a putative physiological maximum despite ongoing p27Kip1 transgene expression.
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