Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease
D Armao, RM Bailey, TW Bouldin, Y Kim… - Clinical Autonomic …, 2016 - Springer
D Armao, RM Bailey, TW Bouldin, Y Kim, SJ Gray
Clinical Autonomic Research, 2016•SpringerPurpose 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 …
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 …
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.
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