Phenotypes Associated with This Genotype

Genotype
MGI:5796775

• Allelic Composition: Tg(Ins2-GLUD1*H454Y)1Csta/0
• Genetic Background: involves: C57BL/6 * SJL

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

mortality/aging

decreased survivor rate ( J:113458 )

• 35% survival at 1 month of age compared to 49% in controls

• survival rates are similar to wild-type mice at 4 months of age

homeostasis/metabolism

increased insulin secretion ( J:113458 )

• base-line insulin secretion in islets is initially elevated but declines close to normal levels after 50 min of glucose perifusion

• islets are more sensitive to leucine- and glutamine-stimulated insulin secretion but have decreased response to glucose stimulation

• islets exhibit enhanced insulin release in response to exposure of a complete mixture of amino acids compared to control islets which are insensitive to an amino acid ramp

• treatment with 6-diazo-5-oxo-L-norleucine to inhibit glutaminase completely abolishes islet responsiveness to glutamine stimulation

hypoglycemia ( J:113458 )

• random blood glucose concentrations are lower after 12 weeks of age

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:113458 )

• 10 mM glutamine alone causes an increase of intracellular calcium in mutant islets but not control islets

• islets show increased basal ATP/ADP ratio and also a higher ATP/ADP ratio in the presence of 10 mM glutamine

increased insulin secretion ( J:113458 )

• base-line insulin secretion in islets is initially elevated but declines close to normal levels after 50 min of glucose perifusion

• islets are more sensitive to leucine- and glutamine-stimulated insulin secretion but have decreased response to glucose stimulation

• islets exhibit enhanced insulin release in response to exposure of a complete mixture of amino acids compared to control islets which are insensitive to an amino acid ramp

• treatment with 6-diazo-5-oxo-L-norleucine to inhibit glutaminase completely abolishes islet responsiveness to glutamine stimulation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyperinsulinemic hypoglycemia		DOID:13317	OMIM:PS256450	J:113458