Mice lacking the transcription factor Ikaros display behavioral alterations of an anti-depressive phenotype

Exp Neurol. 2008 May;211(1):107-14. doi: 10.1016/j.expneurol.2008.01.014. Epub 2008 Feb 5.

Abstract

The Ikaros (Ik) family of transcription factors has critical functions in immune regulation, lymphohematopoiesis and the hypothalamic-pituitary axis. Ik influences cell fate decisions through transcriptional activation of target genes and its interaction with chromatin remodeling complexes. While Ik is well-described in the lymphoid system and pituitary, its presence and function in the brain has received limited attention to date. This study describes the transient spatio-temporal expression of Ik in striatal medium spiny neurons of the developing murine CNS. To determine the impact of Ik deficiency, standardized behavioral tests were performed. In the elevated plus-maze and contextual fear conditioning tests, homozygous Ik-deficient mice performed similarly to wild-type or heterozygote mice. However, significant differences were observed in Ik-null mice in several behavioral tests. Pinch-induced catalepsy was markedly extended. In the Porsolt forced swim test, Ik-null mice showed reduced immobility, consistent with an anti-depressive effect. The acoustic startle response of Ik-null mice was also markedly diminished. Our findings extend the role of the Ikaros zinc-finger protein to the maturation and differentiation of striatal medium spiny neurons and indicate important actions for Ik in the development of neurocognitive functions and affecting depressive behaviors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal / physiology*
  • Conditioning, Psychological / physiology
  • Corpus Striatum / anatomy & histology
  • Corpus Striatum / embryology
  • Corpus Striatum / growth & development
  • Corpus Striatum / pathology
  • Depression* / genetics
  • Depression* / pathology
  • Depression* / physiopathology
  • Disease Models, Animal
  • Embryo, Mammalian
  • Fear / physiology
  • Female
  • Gene Expression Regulation, Developmental
  • Ikaros Transcription Factor / deficiency*
  • Inhibition, Psychological
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Muscle Rigidity / genetics
  • Neurons / pathology
  • Phenotype*
  • Reflex, Startle / genetics
  • Swimming

Substances

  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor