RGD Reference Report - Platelet and myeloid cell phenotypes in a rat model of Fabry disease. - Rat Genome Database

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Platelet and myeloid cell phenotypes in a rat model of Fabry disease.

Authors: Kanack, Adam J  Aoki, Kazuhiro  Tiemeyer, Michael  Dahms, Nancy M 
Citation: Kanack AJ, etal., FASEB J. 2021 Aug;35(8):e21818. doi: 10.1096/fj.202001727RR.
RGD ID: 401976418
Pubmed: PMID:34320241   (View Abstract at PubMed)
PMCID: PMC8341388   (View Article at PubMed Central)
DOI: DOI:10.1096/fj.202001727RR   (Journal Full-text)

Fabry disease results from a deficiency of the lysosomal enzyme ⍺-Galactosidase-A (⍺-Gal A) and is estimated to occur in approximately 1:4100 live births. Characteristic of the disease is the accumulation of α-Gal-A substrates, primarily the glycosphingolipids (GSLs) globotriaosylceramide and globotriaosylsphingosine. Thrombotic events are a significant concern for Fabry patients, with strokes contributing to a significant decrease in overall lifespan. Currently, the mechanisms underlying the increased risk of thrombotic events experienced by Fabry patients are incompletely defined. Using a rat model of Fabry disease, we provide an improved understanding of the mechanisms linking GSL accumulation to thrombotic risk. We found that ⍺-Gal A-deficient rats accumulate myeloid-derived leukocytes at sites of GSL accumulation, including in the bone marrow and circulation, and that myeloid-derived leukocyte and megakaryocyte populations were prominent among cell types that accumulated GSLs. In the circulation, ⍺-Gal A-deficient rats had increases in cytokine-producing cell types and a corresponding elevation of pro-inflammatory cytokines. Lastly, circulating platelets from ⍺-Gal A-deficient rats accumulated a similar set of ⍺-Galactosidase-A substrates as was observed in megakaryocytes in the bone marrow, and exhibited increased platelet binding to fibrinogen in microfluidic and flow cytometric assays.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DA-Glaem2McwiRatFabry disease MODELIMP compared to wild typeRGD 
GLAHumanFabry disease  ISOGla (Rattus norvegicus)compared to wild typeRGD 
GlaMouseFabry disease  ISOGla (Rattus norvegicus)compared to wild typeRGD 
GlaRatFabry disease  IMP compared to wild typeRGD 
Glaem2McwiRatFabry disease  IMP compared to wild typeRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GlaRatglycosphingolipid catabolic process  IMP  RGD 
GlaRatplatelet activation  IMP  RGD 
GlaRatplatelet aggregation  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DA-Glaem2McwiRatabnormal circulating cytokine level  IMP compared to wild typeRGD 
GlaRatabnormal circulating cytokine level  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal circulating cytokine level  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal glycosphingolipid level  IMP compared to wild typeRGD 
GlaRatabnormal glycosphingolipid level  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal glycosphingolipid level  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal lysosome morphology  IMP compared to wild typeRGD 
GlaRatabnormal lysosome morphology  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal lysosome morphology  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal megakaryocyte progenitor cell morphology  IMP compared to wild typeRGD 
GlaRatabnormal megakaryocyte progenitor cell morphology  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal megakaryocyte progenitor cell morphology  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal myeloid cell number  IMP compared to wild typeRGD 
GlaRatabnormal myeloid cell number  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal myeloid cell number  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal myeloid leukocyte morphology  IMP compared to wild typeRGD 
GlaRatabnormal myeloid leukocyte morphology  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal myeloid leukocyte morphology  IMP compared to wild typeRGD 
GlaRatabnormal platelet activation  IMP  RGD 
GlaRatabnormal platelet aggregation  IMP  RGD 
DA-Glaem2McwiRatabnormal platelet morphology  IMP compared to wild typeRGD 
GlaRatabnormal platelet morphology  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal platelet morphology  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal reticulocyte cell number  IMP compared to wild typeRGD 
GlaRatabnormal reticulocyte cell number  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal reticulocyte cell number  IMP compared to wild typeRGD 
DA-Glaem2McwiRatabnormal reticulocyte morphology  IMP compared to wild typeRGD 
GlaRatabnormal reticulocyte morphology  IMP compared to wild typeRGD 
Glaem2McwiRatabnormal reticulocyte morphology  IMP compared to wild typeRGD 
DA-Glaem2McwiRatdecreased mean corpuscular hemoglobin  IMP compared to wild typeRGD 
GlaRatdecreased mean corpuscular hemoglobin  IMP compared to wild typeRGD 
Glaem2McwiRatdecreased mean corpuscular hemoglobin  IMP compared to wild typeRGD 
DA-Glaem2McwiRatdecreased mean corpuscular volume  IMP compared to wild typeRGD 
GlaRatdecreased mean corpuscular volume  IMP compared to wild typeRGD 
Glaem2McwiRatdecreased mean corpuscular volume  IMP compared to wild typeRGD 
DA-Glaem2McwiRatincreased circulating interleukin-17 level  IMP compared to wild typeRGD 
GlaRatincreased circulating interleukin-17 level  IMP compared to wild typeRGD 
Glaem2McwiRatincreased circulating interleukin-17 level  IMP compared to wild typeRGD 
DA-Glaem2McwiRatincreased circulating tumor necrosis factor level  IMP compared to wild typeRGD 
GlaRatincreased circulating tumor necrosis factor level  IMP compared to wild typeRGD 
Glaem2McwiRatincreased circulating tumor necrosis factor level  IMP compared to wild typeRGD 
DA-Glaem2McwiRatincreased erythrocyte cell number  IMP compared to wild typeRGD 
GlaRatincreased erythrocyte cell number  IMP compared to wild typeRGD 
Glaem2McwiRatincreased erythrocyte cell number  IMP compared to wild typeRGD 
DA-Glaem2McwiRatincreased macrophage cell number  IMP compared to wild typeRGD 
GlaRatincreased macrophage cell number  IMP compared to wild typeRGD 
Glaem2McwiRatincreased macrophage cell number  IMP compared to wild typeRGD 
DA-Glaem2McwiRatlysosomal protein accumulation  IMP compared to wild typeRGD 
GlaRatlysosomal protein accumulation  IMP compared to wild typeRGD 
Glaem2McwiRatlysosomal protein accumulation  IMP compared to wild typeRGD 
DA-Glaem2McwiRatthrombocytosis  IMP compared to wild typeRGD 
GlaRatthrombocytosis  IMP compared to wild typeRGD 
Glaem2McwiRatthrombocytosis  IMP compared to wild typeRGD 
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