Phenotypes Associated with This Genotype

Genotype
MGI:3614209

• Allelic Composition: Wfs1^tm1Perm/Wfs1^tm1Perm; Tg(Ins2-cre)23Herr/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * CBA/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body weight ( J:104712 )

• at 24 weeks of age, but not at 16, have lower weights

homeostasis/metabolism

abnormal glucose homeostasis ( J:104712 )

• both fasting and fed glucose:insulin ratios are elevated

• develop diabetes

decreased insulin secretion ( J:104712 )

• impaired glucose-stimulated insulin secretion

hyperglycemia ( J:104712 )

• progressive development of hyperglycemia

• fed glucose concentrations are higher at 24 weeks of age, but mean fasted glucose concentrations are normal

decreased circulating insulin level ( J:104712 )

• fasting insulin levels are significantly reduced at 12 weeks of age and fed insulin levels are reduced at 12 and 24 weeks of age

impaired glucose tolerance ( J:104712 )

• 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

abnormal pancreatic islet morphology ( J:104712 )

• 2.5-fold increase in caspase 3-positive nuclei in islets, indicating increased apoptosis

decreased pancreatic beta cell mass ( J:104712 )

• reduction of beta cell mass is seen at 24 weeks of age

decreased pancreatic beta cell number ( J:104712 )

• reduction of the beta cell:pancreas ratio is seen at 24 weeks of age

disorganized pancreatic islets ( J:104712 )

• 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

abnormal pancreatic beta cell physiology ( J:104712 )

• secretory granules are reduced in beta cells and majority of cells exhibit abundant dilated ER, indicating increased ER stress in beta cells

decreased insulin secretion ( J:104712 )

• impaired glucose-stimulated insulin secretion

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wolfram syndrome 1		DOID:0110629	OMIM:222300	J:104712