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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Apoptosis
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Cell Cycle
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Cell Cycle Proteins*
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Central Nervous System / cytology
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Central Nervous System / metabolism
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Central Nervous System / physiology*
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Cerebral Cortex / metabolism
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Cyclin-Dependent Kinase Inhibitor p27
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Dose-Response Relationship, Drug
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Doxycycline / pharmacology
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Epithelium
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G1 Phase
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Gene Expression
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Mice
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Mice, Transgenic
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Microtubule-Associated Proteins / biosynthesis*
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Microtubule-Associated Proteins / genetics
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Mitosis
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Models, Biological
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Neocortex / cytology
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Neocortex / metabolism
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Neocortex / physiology
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Stem Cells
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Transgenes
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Tumor Suppressor Proteins*
Substances
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Anti-Bacterial Agents
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Microtubule-Associated Proteins
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Doxycycline