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Clinical Autonomic Research

, Volume 26, Issue 4, pp 307–313 | Cite as

Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease

  • Diane Armao
  • Rachel M. Bailey
  • Thomas W. Bouldin
  • Yongbaek Kim
  • Steven J. Gray
Short Communication

Abstract

Purpose

Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood.

Methods

Routine histology and immunohistochemistry was performed on GAN KO mouse specimens taken at various ages. Enteric dysfunction was assessed by quantifying the frequency, weight, and water content of defecation in GAN KO mice.

Results

Histological examination of the enteric, parasympathetic and sympathetic ANS of GAN KO mice revealed pronounced and widespread neuronal perikaryal intermediate filament inclusions. These neuronal inclusions served as an easily identifiable, early marker of GAN in young GAN KO mice. Functional studies identified an age-dependent alteration in fecal weight and defecation frequency in GAN KO mice.

Conclusions

For the first time in the GAN KO mouse model, we described the early, pronounced and widespread neuropathologic features involving the ANS. In addition, we provided evidence for a clinical autonomic phenotype in GAN KO mice, reflected in abnormal gastrointestinal function. These findings in GAN KO mice suggest that consideration should be given to ANS involvement in human GAN, especially when considering treatments and patient care.

Keywords

Giant axonal neuropathy Intermediate filaments Gigaxonin Autonomic nervous system Neurodegenerative disease 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

10286_2016_365_MOESM1_ESM.pdf (318 kb)
Supplementary material 1 (PDF 317 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Diane Armao
    • 1
    • 2
  • Rachel M. Bailey
    • 3
  • Thomas W. Bouldin
    • 1
  • Yongbaek Kim
    • 4
  • Steven J. Gray
    • 3
    • 5
  1. 1.Department of Pathology and Laboratory MedicineUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Department of RadiologyUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Gene Therapy CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  4. 4.Research Institute for Veterinary Sciences and Laboratory of Clinical Pathology, College of Veterinary MedicineSeoul National UniversitySeoulSouth Korea
  5. 5.Department of OphthalmologyUniversity of North Carolina at Chapel HillChapel HillUSA

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