TY - JOUR
T1 - Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse
T2 - implications for human disease
AU - Armao, Diane
AU - Bailey, Rachel M.
AU - Bouldin, Thomas W.
AU - Kim, Yongbaek
AU - Gray, Steven J.
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Autonomic nervous system
KW - Giant axonal neuropathy
KW - Gigaxonin
KW - Intermediate filaments
KW - Neurodegenerative disease
UR - http://www.scopus.com/inward/record.url?scp=84976512768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84976512768&partnerID=8YFLogxK
U2 - 10.1007/s10286-016-0365-7
DO - 10.1007/s10286-016-0365-7
M3 - Article
C2 - 27369358
AN - SCOPUS:84976512768
SN - 0959-9851
VL - 26
SP - 307
EP - 313
JO - Clinical Autonomic Research
JF - Clinical Autonomic Research
IS - 4
ER -