Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT/enhancer binding protein delta.
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.
Sterneck
E
E
Eukaryotic Transcriptional Regulation Section, Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
Paylor
R
R
Jackson-Lewis
V
V
Libbey
M
M
Przedborski
S
S
Tessarollo
L
L
Crawley
J N
JN
Johnson
P F
PF
D000818:Animals; D001921:Brain / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D003214:Conditioning, Classical; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D007858:Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; C497253:Cebpd protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta