Heterozygosity for Nuclear Factor One X Affects Hippocampal-dependent Behaviour in Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jun 19

PMID 23776487

Citations 9

Authors

Lachlan Harris

Chantelle Dixon

Kathleen Cato

Yee Hsieh Evelyn Heng

Nyoman D Kurniawan

Jeremy F P Ullmann

Andrew L Janke

Richard M Gronostajski

Linda J Richards

Thomas H J Burne

Michael Piper

Affiliations

Soon will be listed here.

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.

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