Phenotypes Associated with This Genotype

Genotype
MGI:5883576

• Allelic Composition: Senp1^tm1.1Eyeh/Senp1^tm1.1Eyeh; Tg(Pdx1-cre)6Tuv/0
• Genetic Background: involves: C57BL/6

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

homeostasis/metabolism

decreased insulin secretion ( J:226392 )

♂ • in vitro, islets isolated from male mice exhibit an impaired secretory response to glucose (16.7 mM) and KCl (30 mM) in a perifusion assay; the area under the curve (AUC) of the responses to glucose and KCl is reduced

♂ • when K_ATP channels are held open with diazoxide (100 uM), isolated islets show a blunted secretory response to KCl (30 mM) at 16.7 mM glucose

♂ • impaired insulin secretion is likely due to impaired glucose-dependent amplification of exocytosis

♂ • however, the insulin content of mutant islets is unchanged

decreased circulating insulin level ( J:226392 )

♂ • male mice show a significant reduction in the plasma insulin response to oral glucose relative to control littermates

♂ • however, islet morphology and alpha and beta cell mass is normal at 14 weeks of age

impaired glucose tolerance ( J:226392 )

♂ • male mice are glucose intolerant following an oral glucose challenge at 6 and 12 weeks of age

♂ • however, insulin tolerance is similar to that in control littermates

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:226392 )

♂ • pancreatic beta cells exhibit loss of the glucose-dependent amplification of insulin exocytosis and fail to respond to NADPH and glutathione (GSH), unlike control beta cells

♂ • impaired glucose-dependent amplification of exocytosis can be rescued by reintroduction of the SENP1 catalytic domain (cSENP1) via the patch pipette

♂ • action potential firing is only modestly altered in beta cells, although islet intracellular Ca²⁺ responses remain largely normal

decreased insulin secretion ( J:226392 )

♂ • in vitro, islets isolated from male mice exhibit an impaired secretory response to glucose (16.7 mM) and KCl (30 mM) in a perifusion assay; the area under the curve (AUC) of the responses to glucose and KCl is reduced

♂ • when K_ATP channels are held open with diazoxide (100 uM), isolated islets show a blunted secretory response to KCl (30 mM) at 16.7 mM glucose

♂ • impaired insulin secretion is likely due to impaired glucose-dependent amplification of exocytosis

♂ • however, the insulin content of mutant islets is unchanged

nervous system

impaired ability to fire action potentials ( J:226392 )

♂ • action potential firing is only modestly affected in pancreatic beta cells, as shown by a small but significant reduction in action potential height with no significant differences in inter-spike membrane potential

♂ • however, islet intracellular Ca²⁺ responses remain largely normal

growth/size/body

growth/size/body region phenotype ( J:226392 )

♂N • male mice exhibit normal body weight between 6 and 14 weeks of age