Neurobehavioral basis of the impaired nurturing in mice lacking the immediate early gene FosB

Brain Res. 2008 May 23:1211:57-71. doi: 10.1016/j.brainres.2008.02.100. Epub 2008 Mar 18.


The transcription factor FosB is induced in neurons of the medial preoptic area (MPOA) during parenting, through activation of the extracellular signal-regulated kinase (ERK). FosB mutant (-/-) postpartum mice and virgin mice that are exposed to pups show defective nurturing behavior. The FosB (-/-) MPOA fails to fully up-regulate SPRY1 and Rad, the feedback regulators of ERK and calcium signaling, respectively. Here we studied FosB function by examining the gene expression profiles and the behavioral characteristics of FosB (-/-) mice. We found that FosB (-/|-) mice exhibited not only decreased parenting but also decreased infanticide compared with (+/) littermates. We then performed gene expression analysis in the MPOA of FosB (-/-) mice compared with the wild-type littermates. We found up-regulation of glial fibrillary acidic protein (GFAP), C4, and Ela1 mRNA in the MPOA of FosB (-/-) mice; all of these gene products were implicated in general neuropathological conditions. Immunohistochemical analysis showed that up-regulation of GFAP was not restricted to MPOA but extended throughout the forebrain, including the cerebral cortex and striatum. Such pervasive GFAP up-regulation suggested that FosB (-/-) mice might have other behavioral abnormalities than nurturing. Indeed, these mice showed a clear alteration in emotionality, detected by the acoustic startle, elevated plus maze, and passive avoidance tests. These results suggest that FosB (-/-) mice have broader neurobehavioral dysfunctions, with which the nurturing defect might share the common mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Behavior, Animal / physiology
  • Female
  • Genes, fos / genetics*
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Hydrocortisone / blood
  • Male
  • Maternal Behavior / physiology*
  • Mice
  • Mice, Knockout
  • Motor Activity / physiology
  • Neurosecretory Systems / physiology
  • Oligonucleotide Array Sequence Analysis
  • Preoptic Area / physiology*
  • Proto-Oncogene Proteins c-fos / genetics*
  • Reflex, Startle / genetics
  • Reflex, Startle / physiology
  • Restraint, Physical
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Psychological / genetics
  • Stress, Psychological / physiopathology
  • Up-Regulation / genetics
  • Up-Regulation / physiology


  • Glial Fibrillary Acidic Protein
  • Proto-Oncogene Proteins c-fos
  • Hydrocortisone