Heterozygosity for nuclear factor one x affects hippocampal-dependent behaviour in mice

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 Nu...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e65478-e65478
Main Authors: Harris, Lachlan, Dixon, Chantelle, Cato, Kathleen, Heng, Yee Hsieh Evelyn, Kurniawan, Nyoman D, Ullmann, Jeremy F P, Janke, Andrew L, Gronostajski, Richard M, Richards, Linda J, Burne, Thomas H J, Piper, Michael
Format: Article
Language:English
Subjects:
Animals
Biology
Brain
Cortex
Dentate gyrus
DNA binding proteins
Female
Gene expression
Genes
Genomics
Genotype & phenotype
Heterozygosity
Heterozygote
Hippocampus
Hippocampus - embryology
Hippocampus - metabolism
Immunohistochemistry
Lethality
Magnetic Resonance Imaging
Male
Maze learning
Maze Learning - physiology
Memory
Mental task performance
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Molecular Sequence Data
Morphology
Nervous system
Neurogenesis
NFI Transcription Factors - genetics
NFI Transcription Factors - metabolism
Nuclear factor I
Pregnancy
Rodents
Transcription factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0065478