title: Disruption of CREB function in brain leads to neurodegeneration.
abstract: 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.
authors.affiliation: Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Theo
authors.initials: T
authors.lastname: Mantamadiotis
authors.forename: Thomas
authors.initials: T
authors.lastname: Lemberger
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Bleckmann
authors.forename: Heidrun
authors.initials: H
authors.lastname: Kern
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.forename: Ana
authors.initials: A
authors.lastname: Martin Villalba
authors.forename: François
authors.initials: F
authors.lastname: Tronche
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellendonk
authors.forename: Daniel
authors.initials: D
authors.lastname: Gau
authors.forename: Josef
authors.initials: J
authors.lastname: Kapfhammer
authors.forename: Christiane
authors.initials: C
authors.lastname: Otto
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmid
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000502:physiology*; D003342:Corpus Striatum / Q000473:pathology; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D012097:Repressor Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C115163:CREB1 protein, human; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D010455:Peptides; D012097:Repressor Proteins; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator; C097188:polyglutamine