Mouse Genome Informatics
cn
    Wfs1tm1Perm/Wfs1tm1Perm
Tg(Ins2-cre)23Herr/0

involves: 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
growth/size/body
• at 24 weeks of age, but not at 16, have lower weights

homeostasis/metabolism
• both fasting and fed glucose:insulin ratios are elevated
• develop diabetes
• impaired glucose-stimulated insulin secretion
• progressive development of hyperglycemia
• fed glucose concentrations are higher at 24 weeks of age, but mean fasted glucose concentrations are normal
• fasting insulin levels are significantly reduced at 12 weeks of age and fed insulin levels are reduced at 12 and 24 weeks of age
• progressive glucose intolerance, with mild glucose intolerance 60 min after glucose injection by 12 weeks of age and significant glucose intolerance 30, 60, and 120 min after glucose injection by 16 weeks of age

endocrine/exocrine glands
• 2.5-fold increase in caspase 3-positive nuclei in islets, indicating increased apoptosis
• reduction of beta cell mass is seen at 24 weeks of age
• reduction of the beta cell:pancreas ratio is seen at 24 weeks of age
• asymmetry and disruption of islet architecture is apparent at 12 weeks of age, with an alteration of the ratio of beta to non-beta cells within the islet
• secretory granules are reduced in beta cells and majority of cells exhibit abundant dilated ER, indicating increased ER stress in beta cells
• impaired glucose-stimulated insulin secretion

Mouse Models of Human Disease
OMIM IDRef(s)
Wolfram Syndrome 1; WFS1 222300 J:104712