Phenotypes associated with this allele

• Allele Symbol: Tg(Slc2a4-cre)546Dac
• Allele Name: transgene insertion 546, Domenico Accili
• Allele ID: MGI:4941207
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Insr^tm1Khn/Insr^tm1Khn Tg(Slc2a4-cre)546Dac/0	involves: 129S4/SvJaeSor * C57BL/6 * FVB	MGI:4941586

Genotype
MGI:4941586

cn1

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Tg(Slc2a4-cre)546Dac/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * FVB

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

growth/size/body

abnormal lean body mass ( J:169404 )

• diabetic mutants show reduced lean body mass but normal locomotion

decreased body weight ( J:169404 )

• 16-week-old males exhibit a 19% decrease in body weight relative to controls; reduction affects lean and fat mass equally, and plasma leptin levels are normal

• diabetic mutants have significantly lower body weights than controls or non-diabetic mutants

postnatal growth retardation ( J:169404 )

• body weight of mutants is normal as weanlings, but mice show persistent growth retardation from that time point onward

adipose tissue

abnormal brown adipose tissue morphology ( J:169404 )

• tissue shows striking disruption of multilocular structure in mutants; this is more pronounced in diabetic mutants

increased brown fat cell lipid droplet size ( J:169404 )

• size is increased in mutants; this is more pronounced in diabetic mutants

abnormal epididymal fat pad morphology ( J:169404 )

• epididymal white adipose tissue has a heterogeneous appearance compared to controls

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:169404 )

• euglycemic mutants display beta cell hyperplasia, but otherwise islet structure is normal

abnormal pancreatic beta cell morphology ( J:169404 )

• euglycemic mutants display beta cell hyperplasia, but otherwise islet structure is normal

decreased pancreatic beta cell number ( J:169404 )

• diabetic mutants show spotted pattern of loss of insulin immunoreactivity in pancreatic islets

liver/biliary system

decreased liver glycogen level ( J:169404 )

• glycogen depletion in liver is observed only in diabetic mutant animals; non-diabetic mutants have normal-appearing livers

hepatic steatosis ( J:169404 )

• this is observed only in diabetic mutant animals; non-diabetic mutants have normal-appearing livers

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:169404 )

N • fasting plasma glucagon and beta-hydroxyl butyrate levels are similar to controls

increased circulating free fatty acids level ( J:169404 )

• clamp hyperinsulinemia suppresses free fatty acid levels by 43% but has no effect on GIRKO (Glut4-cre-driven InsR knockout) mutants

increased oxygen consumption ( J:169404 )

• diabetic mutants show increased oxygen consumption when normalized to body weight compared to controls

abnormal glucose homeostasis ( J:169404 )

• during hyperinsulinemic phase of (euglycemic-hyperglycemic) clamp experiments on 13-15 week-old mice, rate of glucose infusion to maintain euglycemia is increased 52% relative to controls (suggesting impaired glucose clearance)

• basal hepatic glucose production is increased by 32% and hyperinsulinemia cannot suppress it (suggesting hepatic insulin resistance)

• glucose disappearance is reduced by 28% and glycolysis is decreased by 33% compared to controls, while glycogen synthesis shows a downward trend

• insulin-dependent glucose uptake is reduced by 34% in muscle

increased circulating glucose level ( J:169404 )

• under basal conditions, mice show slightly elevated blood glucose levels (119 vs 87 mg/dl)

hyperglycemia ( J:169404 )

• at 5 weeks, a subset of mice (male and female) show hyperglycemia in the fed state

• prevalence of diabetes (glycemia > +2 standard deviations) in males increases from 20% at 5 weeks to 25% at 12 weeks and 46% at 24 weeks; in females, diabetes prevalence remains around 10% in 5-12 week-old mice

increased circulating insulin level ( J:169404 )

• subset of mice exhibit hyperinsulinemia in fed and fasted state at 12 weeks

impaired glucose tolerance ( J:169404 )

• at 12-13 weeks, males show mild glucose intolerance

decreased liver glycogen level ( J:169404 )

• glycogen depletion in liver is observed only in diabetic mutant animals; non-diabetic mutants have normal-appearing livers

insulin resistance ( J:169404 )

• 12-13 week old females show mild insulin resistance

behavior/neurological

abnormal circadian feeding behavior ( J:169404 )

• non-diabetic mutants show reduced food consumption during the light phase compared to controls (26% vs 34% in controls)