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: PMID:29563343   (View Abstract at PubMed)
PMCID: PMC5926911   (View Article at PubMed Central)
DOI: DOI:10.1172/jci.insight.99171   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Fabry disease  IMP 150429980; 150429980compared to wild typeRGD 
Fabry disease  ISOGla (Rattus norvegicus)150429980; 150429980 RGD 
Fabry disease  IMP 150429980 RGD 
lysosomal storage disease  IMP 150429980; 150429980compared to wild typeRGD 
lysosomal storage disease  ISOGla (Rattus norvegicus)150429980; 150429980 RGD 
lysosomal storage disease  IMP 150429980 RGD 
Pain  IMP 150429980; 150429980; 150429980compared to wild typeRGD 
Pain  ISOGla (Rattus norvegicus)150429980; 150429980 RGD 
Pain treatmentIMP 150429980Allyl isothiocyanate (XCO:0000608)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

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)

Strains
DA-Glaem2Mcwi  (NA)


Additional Information