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Proc Natl Acad Sci U S A. 2001 May 22;98(11):6435-40.

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

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  • 1Department of Developmental Neurobiology, Central Nervous System Signaling Laboratory, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.


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.

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