Overexpression of p27 ^Kip1 lengthens the G ₁ phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells

Abstract

We describe a mouse model in which p27(Kip1) 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 G(1) phase of the cell cycle is estimated to increase from 9 to 13 h in the neocortical neuroepithelium, the maximum G(1) phase length attainable in this proliferative population in normal mice. Thus our data establish a direct link between p27(Kip1) and control of G(1) phase length in the mammalian central nervous system and unveil intrinsic mechanisms that constrain the G(1) phase length to a putative physiological maximum despite ongoing p27(Kip1) transgene expression.