Pathological aggression in "Fierce" mice corrected by human nuclear receptor 2E1

Brett S. Abrahams, Melvin C.H. Kwok, Eric Trinh, Saeed Budaghzadeh, Sazzad M. Hossain, Elizabeth M. Simpson

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

"Fierce" mice, homozygous for the deletion of nuclear receptor 2E1l (NR2E1), show abnormal brain-eye development and pathological aggression. To evaluate functional equivalency between mouse and human NR2E1, we generated mice transgenic for a genomic clone spanning the human NR2E1 locus and bred these animals to fierce mice deleted for the corresponding mouse gene. In fierce mutants carrying human NR2E1, structural brain defects were eliminated and eye abnormalities ameliorated. Excitingly, behavior in these "rescue" mice was indistinguishable from controls. Because no artificial promoter was used to drive transgene expression, promoter and regulatory elements within the human NR2E1 clone are functional in mouse. Normal behavior in rescue animals suggests that mechanisms underlying the behavioral abnormalities in fierce mice may also be conserved in humans. Our data support the hypothesis that variation at NR2E1 may contribute to human behavioral disorders. Use of this rescue paradigm with other genes will permit the direct evaluation of human genes hypothesized to play a causal role in psychiatric disease but for which evidence is lacking or equivocal.

Original languageEnglish (US)
Pages (from-to)6263-6270
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number27
DOIs
StatePublished - Jul 6 2005

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Keywords

  • 6q21-6q22
  • Behavior
  • Genetic disease
  • Tlx
  • Transgenic rescue
  • Violence

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Abrahams, B. S., Kwok, M. C. H., Trinh, E., Budaghzadeh, S., Hossain, S. M., & Simpson, E. M. (2005). Pathological aggression in "Fierce" mice corrected by human nuclear receptor 2E1. Journal of Neuroscience, 25(27), 6263-6270. https://doi.org/10.1523/JNEUROSCI.4757-04.2005