RGD Reference Report - Neuropathic pain in a Fabry disease rat model. - Rat Genome Database

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Neuropathic pain in a Fabry disease rat model.

Authors: Miller, James J  Aoki, Kazuhiro  Moehring, Francie  Murphy, Carly A  O'Hara, Crystal L  Tiemeyer, Michael  Stucky, Cheryl L  Dahms, Nancy M 
Citation: Miller JJ, etal., JCI Insight. 2018 Mar 22;3(6). pii: 99171. doi: 10.1172/jci.insight.99171.
RGD ID: 150429980
Pubmed: (View Article at PubMed) PMID:29563343
DOI: Full-text: DOI:10.1172/jci.insight.99171

Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge. Fabry rats had substantial serum and tissue accumulation of α-galactosyl glycosphingolipids and had pronounced mechanical pain behavior. Additionally, Fabry rat dorsal root ganglia displayed global N-glycan alterations, sensory neurons were laden with inclusions, and sensory neuron somata exhibited prominent sensitization to mechanical force. We found that the cation channel transient receptor potential ankyrin 1 (TRPA1) is sensitized in Fabry rat sensory neurons and that TRPA1 antagonism reversed the behavioral mechanical sensitization. This study points toward TRPA1 as a potentially novel target to treat the pain experienced by patients with Fabry disease.

Disease Annotations    
Fabry disease  (IMP,ISO)
lysosomal storage disease  (IMP,ISO)
Pain  (IMP,ISO)

Phenotype Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Gla  (galactosidase, alpha)
Glaem2Mcwi  (galactosidase, alpha; CRISPR/Cas9 system induced mutant 2, Medical College of Wisconsin)

Genes (Mus musculus)
Gla  (galactosidase, alpha)

Genes (Homo sapiens)
GLA  (galactosidase alpha)

DA-Glaem2Mcwi  (NA)

Additional Information