Nature genetics, 2002-05, Vol.31 (1), p.47-54
2002
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- Autor(en) / Beteiligte
- Titel
- Disruption of CREB function in brain leads to neurodegeneration
- Ist Teil von
- Nature genetics, 2002-05, Vol.31 (1), p.47-54
- Ort / Verlag
- London: Nature Publishing Group
- Erscheinungsjahr
- 2002
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Control of cellular survival and proliferation is dependent on extracellular signals and is a prerequisite for ordered tissue development and maintenance. Activation of the cAMP responsive element binding protein (CREB) by phosphorylation has been implicated in the survival of mammalian cells. To define its roles in the mouse central nervous system, we disrupted Creb1 in brain of developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-) background and lacking Creb in the central nervous system during development show extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1 and Crem are disrupted in the postnatal forebrain show progressive neurodegeneration in the hippocampus and in the dorsolateral striatum. The striatal phenotype is reminiscent of Huntington disease and is consistent with the postulated role of CREB-mediated signaling in polyglutamine-triggered diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1061-4036eISSN: 1546-1718DOI: 10.1038/ng882Titel-ID: cdi_proquest_miscellaneous_856754144
- Format
- –
- Schlagworte
- Animals, Apoptosis, Binding proteins, Biological and medical sciences, Brain, Brain - physiology, Cell death, Cell differentiation, maturation, development, hematopoiesis, Cell physiology, Classical genetics, quantitative genetics, hybrids, Corpus Striatum - pathology, Cyclic AMP Response Element Modulator, Cyclic AMP Response Element-Binding Protein, Degeneration, DNA-Binding Proteins - deficiency, DNA-Binding Proteins - genetics, DNA-Binding Proteins - physiology, Female, Fundamental and applied biological sciences. Psychology, Gene expression, Genetic aspects, Genetics, Genetics of eukaryotes. Biological and molecular evolution, Health aspects, Humans, Huntington Disease - etiology, Huntington Disease - genetics, Huntington Disease - pathology, Kinases, Male, Mice, Mice, Knockout, Mice, Transgenic, Molecular and cellular biology, Mutation, Nerve Degeneration - etiology, Nerve Degeneration - genetics, Nerve Degeneration - pathology, Nervous system, Neurodegeneration, Peptides - genetics, Phenotype, Phosphorylation, Proteins, Repressor Proteins, Signal Transduction, Transcription factors, Transcription Factors - deficiency, Transcription Factors - genetics, Transcription Factors - physiology, Vertebrata