title: Heterozygosity for nuclear factor one x affects hippocampal-dependent behaviour in mice.
abstract: Identification of the genes that regulate the development and subsequent functioning of the hippocampus is pivotal to understanding the role of this cortical structure in learning and memory. One group of genes that has been shown to be critical for the early development of the hippocampus is the Nuclear factor one (Nfi) family, which encodes four site-specific transcription factors, NFIA, NFIB, NFIC and NFIX. In mice lacking Nfia, Nfib or Nfix, aspects of early hippocampal development, including neurogenesis within the dentate gyrus, are delayed. However, due to the perinatal lethality of these mice, it is not clear whether this hippocampal phenotype persists to adulthood and affects hippocampal-dependent behaviour. To address this we examined the hippocampal phenotype of mice heterozygous for Nfix (Nfix (+/-)), which survive to adulthood. We found that Nfix (+/-) mice had reduced expression of NFIX throughout the brain, including the hippocampus, and that early hippocampal development in these mice was disrupted, producing a phenotype intermediate to that of wild-type mice and Nfix(-/-) mice. The abnormal hippocampal morphology of Nfix (+/-) mice persisted to adulthood, and these mice displayed a specific performance deficit in the Morris water maze learning and memory task. These findings demonstrate that the level of Nfix expression during development and within the adult is essential for the function of the hippocampus during learning and memory.
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Harris
authors.forename: Chantelle
authors.initials: C
authors.lastname: Dixon
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cato
authors.forename: Yee Hsieh Evelyn
authors.initials: YH
authors.lastname: Heng
authors.forename: Nyoman D
authors.initials: ND
authors.lastname: Kurniawan
authors.forename: Jeremy F P
authors.initials: JF
authors.lastname: Ullmann
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Janke
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.forename: Thomas H J
authors.initials: TH
authors.lastname: Burne
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
mesh_terms: D000818:Animals; D005260:Female; D006579:Heterozygote; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D051839:NFI Transcription Factors; C497646:Nfia protein, mouse; C484683:Nfib protein, mouse; C497650:Nfix protein, mouse