Mice lacking the transcription factor Ikaros display behavioral alterations of an anti-depressive phenotype.
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.
Kiehl
Tim-Rasmus
TR
Department of Pathology, University Health Network, 610 University Avenue, Toronto, Ontario, Canada. rasmus.kiehl@uhn.on.ca
Fischer
Sandra E
SE
Ezzat
Shereen
S
Asa
Sylvia L
SL
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D003863:Depression / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005239:Fear / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051740:Ikaros Transcription Factor / Q000172:deficiency*; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009127:Muscle Rigidity / Q000235:genetics; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D013216:Reflex, Startle / Q000235:genetics; D013550:Swimming
C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor