title: FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔFosB.
abstract: BACKGROUND
  Molecular mechanisms underlying stress tolerance and vulnerability are incompletely understood. The fosB gene is an attractive candidate for regulating stress responses, because ΔFosB, an alternative splice product of the fosB gene, accumulates after repeated stress or antidepressant treatments. On the other hand, FosB, the other alternative splice product of the fosB gene, expresses more transiently than ΔFosB but exerts higher transcriptional activity. However, the functional differences of these two fosB products remain unclear.
  
  
  METHODS
  We established various mouse lines carrying three different types of fosB allele, wild-type (fosB(+)), fosB-null (fosB(G)), and fosB(d) allele, which encodes ΔFosB but not FosB, and analyzed them in stress-related behavioral tests.
  
  
  RESULTS
  Because fosB(+/d) mice show enhanced ΔFosB levels in the presence of FosB and fosB(d/d) mice show more enhanced ΔFosB levels in the absence of FosB, the function of FosB can be inferred from differences observed between these lines. The fosB(+/d) and fosB(d/d) mice showed increased locomotor activity and elevated Akt phosphorylation, whereas only fosB(+/d) mice showed antidepressive-like behaviors and increased E-cadherin expression in striatum compared with wild-type mice. In contrast, fosB-null mice showed increased depression-like behavior and lower E-cadherin expression.
  
  
  CONCLUSIONS
  These findings indicate that FosB is essential for stress tolerance mediated by ΔFosB. These data suggest that fosB gene products have a potential to regulate mood disorder-related behaviors.
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Yoshinori N
authors.initials: YN
authors.lastname: Ohnishi
authors.forename: Yoko H
authors.initials: YH
authors.lastname: Ohnishi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hokama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nomaru
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tominaga
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Sakumi
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D015820:Cadherins; C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine