-
Disruption of CREB function in brain leads to neurodegeneration.
Mantamadiotis T,
Lemberger T,
Bleckmann SC,
Kern H,
Kretz O,
Martin Villalba A,
Tronche F,
Kellendonk C,
Gau D,
Kapfhammer J,
Otto C,
Schmid W,
Schütz G.
Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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.
PMID: 11967539 [PubMed - indexed for MEDLINE]
-
Cited by 36 PubMed Central articles
-
The Nuclear Transcription Factor CREB: Involvement in Addiction, Deletion Models and Looking Forward.
McPherson CS, Lawrence AJ.
Curr Neuropharmacol. 2007 Sep; 5(3):202-12.
[Curr Neuropharmacol. 2007]
-
Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice.
Sato T, Miura M, Yamada M, Yoshida T, Wood JD, Yazawa I, Masuda M, Suzuki T, Shin RM, Yau HJ, et al.
Hum Mol Genet. 2009 Feb 15; 18(4):723-36. Epub 2008 Nov 27.
[Hum Mol Genet. 2009]
-
Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine.
Bilbao A, Parkitna JR, Engblom D, Perreau-Lenz S, Sanchis-Segura C, Schneider M, Konopka W, Westphal M, Breen G, Desrivieres S, et al.
Proc Natl Acad Sci U S A. 2008 Nov 11; 105(45):17549-54. Epub 2008 Nov 10.
[Proc Natl Acad Sci U S A. 2008]
- » See all...