RGD Reference Report - Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration. - Rat Genome Database

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Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration.

Authors: Plaas, Mario  Seppa, Kadri  Reimets, Riin  Jagomäe, Toomas  Toots, Maarja  Koppel, Tuuliki  Vallisoo, Tuuli  Nigul, Mait  Heinla, Indrek  Meier, Riho  Kaasik, Allen  Piirsoo, Andres  Hickey, Miriam A  Terasmaa, Anton  Vasar, Eero 
Citation: Plaas M, etal., Sci Rep. 2017 Aug 31;7(1):10220. doi: 10.1038/s41598-017-09392-x.
RGD ID: 149735331
Pubmed: (View Article at PubMed) PMID:28860598
DOI: Full-text: DOI:10.1038/s41598-017-09392-x

Wolfram syndrome (WS) is a rare autosomal-recessive disorder that is caused by mutations in the WFS1 gene and is characterized by juvenile-onset diabetes, optic atrophy, hearing loss and a number of other complications. Here, we describe the creation and phenotype of Wfs1 mutant rats, in which exon 5 of the Wfs1 gene is deleted, resulting in a loss of 27 amino acids from the WFS1 protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age. Beta cell mass is reduced in older mutant rats, which is accompanied by decreased glucose-stimulated insulin secretion from 3 months of age. Medullary volume is decreased in older Wfs1-ex5-KO232 rats, with the largest decreases at the level of the inferior olive. Finally, older Wfs1-ex5-KO232 rats show retinal gliosis and optic nerve atrophy at 15 months of age. Electron microscopy revealed axonal degeneration and disorganization of the myelin in the optic nerves of older Wfs1-ex5-KO232 rats. The phenotype of Wfs1-ex5-KO232 rats indicates that they have the core symptoms of WS. Therefore, we present a novel rat model of WS.



Disease Annotations    
cataract  (IMP,ISO)
diabetes mellitus  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Wfs1  (wolframin ER transmembrane glycoprotein)
Wfs1em1Ptsn  (wolframin ER transmembrane glycoprotein; ZFN induced mutant 1)
Wfs1em2Ptsn  (wolframin ER transmembrane glycoprotein; ZFN induced mutant 2)
Wfs1em3Ptsn  (wolframin ER transmembrane glycoprotein; ZFN induced mutant 3)

Genes (Mus musculus)
Wfs1  (wolframin ER transmembrane glycoprotein)

Genes (Homo sapiens)
WFS1  (wolframin ER transmembrane glycoprotein)


Additional Information