Survival of DA neurons is independent of CREM upregulation in absence of CREB.
cAMP response element binding protein (CREB) and the related factors CREM (cAMP response element modulator) and ATF1 (activation transcription factor 1) are bZIP-domain-containing transcription factors activated through cAMP and other signaling pathways. The disruption of CREB function in developing and mature neurons affects their development and survival when associated with loss of CREM. Since dopaminergic (DA) neurons are affected in several neurological diseases, we generated CREB conditional mutants in DA neurons by using a newly generated transgenic Cre line targeting the dopaminergic system (DATCre). Here we report the generation and analysis of mutant mice lacking CREB in DA neurons (CREB(DATCre) mutants). During adulthood, lack of CREB leads to a partial loss of DA neurons. Since CREM is upregulated in absence of CREB, we have introduced this mutation in a CREM-/- genetic background to assess a compensatory role of CREM. Additional inactivation of CREM does not lead to a more severe phenotype.
Parlato
R
R
Department of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
Rieker
C
C
Turiault
M
M
Tronche
F
F
Schütz
G
G
D000818:Animals; D002470:Cell Survival; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation
D017362:Cyclic AMP Response Element-Binding Protein; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP