RGD Reference Report - Rats deficient in α-galactosidase A develop ocular manifestations of Fabry disease. - Rat Genome Database

RGD Reference Report - Rats deficient in α-galactosidase A develop ocular manifestations of Fabry disease. - Rat Genome Database

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Rats deficient in α-galactosidase A develop ocular manifestations of Fabry disease.
Authors:	Miller, James J Aoki, Kazuhiro Reid, Christopher A Tiemeyer, Michael Dahms, Nancy M Kassem, Iris S
Citation:	Miller JJ, etal., Sci Rep. 2019 Jun 28;9(1):9392. doi: 10.1038/s41598-019-45837-1.
RGD ID:	401976417
Pubmed:	PMID:31253878 (View Abstract at PubMed)
PMCID:	PMC6599056 (View Article at PubMed Central)
DOI:	DOI:10.1038/s41598-019-45837-1 (Journal Full-text)
Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A. Ocular findings, such as cornea verticillata, cataracts, and retinal vascular tortuosity, serve as important diagnostic markers. We aimed to evaluate ocular phenotypes in α-galactosidase A-deficient (Fabry) rats and hypothesized that these rats would manifest ocular signs similar to those observed in patients. Slit lamp biomicroscopy was used to evaluate the cornea and lens, and retinal vasculature was examined by fluorescein angiography in WT and Fabry rats. Mass spectrometry was used to characterize and quantify ocular glycosphingolipids, and histology and electron microscopy revealed the location of the glycosphingolipid storage. We found that Fabry rats developed corneal and lenticular opacities to a statistically greater degree than WT rats. Retinal vascular morphology did not appear grossly different, but there was vascular leakage in at least one Fabry rat. Fabry rat eyes accumulated substrates of α-galactosidase A, and these α-galactosyl glycoconjugates were found in corneal keratocytes, lens fibers, and retinal vascular endothelial cells. Electron-dense lamellar inclusions were observed in keratocytes. Because Fabry rats recapitulate many ocular phenotypes observed in patients, they can be used to study disease pathogenesis and determine whether ocular findings serve as noninvasive indicators of therapeutic efficacy.

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Phenotype Annotations Click to see Annotation Detail View

Mammalian Phenotype

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
DA-Gla^em2Mcwi	Rat	abnormal lens fiber morphology	severity	IMP		compared to wild type	RGD
Gla	Rat	abnormal lens fiber morphology	severity	IMP		compared to wild type	RGD
Gla^em2Mcwi	Rat	abnormal lens fiber morphology	severity	IMP		compared to wild type	RGD
DA-Gla^em2Mcwi	Rat	abnormal retina blood vessel morphology		IMP			RGD
Gla	Rat	abnormal retina blood vessel morphology		IMP			RGD
Gla^em2Mcwi	Rat	abnormal retina blood vessel morphology		IMP			RGD
DA-Gla^em2Mcwi	Rat	abnormal sphingolipid level		IMP		in eyes and compared to wild type	RGD
Gla	Rat	abnormal sphingolipid level		IMP		in eyes and compared to wild type	RGD
Gla^em2Mcwi	Rat	abnormal sphingolipid level		IMP		in eyes and compared to wild type	RGD
DA-Gla^em2Mcwi	Rat	cornea opacity	severity	IMP		compared to wild type	RGD
Gla	Rat	cornea opacity	severity	IMP		compared to wild type	RGD
Gla^em2Mcwi	Rat	cornea opacity	severity	IMP		compared to wild type	RGD

Objects Annotated

Genes (Rattus norvegicus)

Gla (galactosidase, alpha)

Gla^em2Mcwi (galactosidase, alpha; CRISPR/Cas9 system induced mutant 2, Medical College of Wisconsin)

Strains

DA-Gla^em2Mcwi (NA)

Additional Information