Cellular and molecular characterization of oxidative stress in olfactory epithelium of harlequin mutant mouse

Radhika A. Vaishnav, Marilyn L. Getchell, Liping Huang, Matthew A. Hersh, Arnold J. Stromberg, Thomas V. Getchell

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Oxidative stress in the olfactory system is a major factor associated with age-related olfactory impairment, although the mechanisms by which this occurs are not completely understood. The Harlequin mutant mouse (Hq/Y), which carries an X-linked recessive mutation in the Aifm1 gene, is a model of progressive oxidative stress-induced neurodegeneration in the cerebellum and retina. To determine whether the Hq/Y mutant mouse is a suitable model of oxidative stress-associated olfactory aging, we investigated cellular and molecular changes in the olfactory epithelium (OE) and olfactory bulb (OB) of 6-month-old male Hq/Y mice compared to those in sex-matched littermate controls (+/Y) and in age- and sex-matched C57BL/6 mice. Immunoreactivity for apoptosis-inducing factor, the protein product of Aifm1, was localized in mature olfactory sensory neurons (mOSNs) in +/Y mice but was rarely detected in Hq/Y mice. Hq/Y mice also exhibited increased lipofuscin autofluorescence and increased immunoreactivity for an oxidative DNA/RNA damage marker in mOSNs and in mitral/tufted cells in the OB and an increased number of cleaved caspase-3 immunoreactive apoptotic cells in the OE. Microarray analysis demonstrated that Aifm1 expression was down-regulated by 80% in the OE of Hq/Y mice compared to that in +/Y mice. Most significantly, regulated genes were classified into functional categories of cell signaling/apoptosis/cell cycle, oxidative stress/aging, and cytoskeleton/extracellular matrix/transport-associated. Analysis with EASE software indicated that the functional categories significantly overrepresented in Hq/Y mice included up-regulated mitochondrial genes and down-regulated cytoskeletal organization- and neurogenesis-related genes. Our results strongly support the Hq/Y mutant mouse being a novel model for mechanistic studies of oxidative stress-associated olfactory aging.

Original languageEnglish
Pages (from-to)165-182
Number of pages18
JournalJournal of Neuroscience Research
Issue number1
StatePublished - Jan 2008


  • 8-hydroxydeoxyguanosine/8-hydroxyguanosine
  • Aifm1
  • Apoptosis-inducing factor
  • Mitochondria, bioinformatics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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