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Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT/enhancer binding protein delta.

Abstract
CCAAT/enhancer binding protein delta (C/EBPdelta) is a transcriptional regulator implicated in the hepatic acute phase response and in adipogenic and myeloid cell differentiation. We found that C/EBPdelta is widely expressed in the peripheral and central nervous systems, including neurons of the hippocampal formation, indicating a role in neural functions. To examine the role of C/EBPdelta in vivo, we generated mice with a targeted deletion of the C/EBPdelta gene. This mutation does not interfere with normal embryonic and postnatal development. Performance in a battery of behavioral tests indicates that basic neurological functions are normal. Furthermore, performance in a Morris water maze task suggests that C/EBPdelta mutant mice have normal spatial learning. However, in the contextual and auditory-cue-conditioned fear task, C/EBPdelta null mice displayed significantly more conditioned freezing to the test context than did wild-type controls, but equivalent conditioning to the auditory cue. These data demonstrate a selectively enhanced contextual fear response in mice carrying a targeted genomic mutation and implicate C/EBPdelta in the regulation of a specific type of learning and memory.
AuthorsE Sterneck, R Paylor, V Jackson-Lewis, M Libbey, S Przedborski, L Tessarollo, J N Crawley, P F Johnson
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 18 Pg. 10908-13 (Sep 01 1998) ISSN: 0027-8424 [Print] United States
PMID9724803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CCAAT-Enhancer-Binding Proteins
  • Cebpd protein, mouse
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • CCAAT-Enhancer-Binding Protein-delta
Topics
  • Animals
  • Brain (metabolism)
  • CCAAT-Enhancer-Binding Protein-delta
  • CCAAT-Enhancer-Binding Proteins
  • Cell Line
  • Conditioning, Classical
  • DNA-Binding Proteins (genetics, physiology)
  • Fear (physiology)
  • Female
  • Gene Deletion
  • Learning
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins (genetics, physiology)
  • Transcription Factors (physiology)

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