Phenotypes associated with this allele

• Allele Symbol: Slc2a4^tm1Abel
• Allele Name: targeted mutation 1, E Dale Abel
• Allele ID: MGI:2182083
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Myhca-cre)1Abel/?	involves: 129S4/SvJae * C57BL/6 * FVB	MGI:3629925
cn2	Slc2a4^tm1Abel/Slc2a4^+ Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * FVB	MGI:3663418
cn3	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * FVB	MGI:3663416
cn4	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Fabp4-cre)1Abel/?	involves: 129S4/SvJae * FVB	MGI:3029364
cn5	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Myhca-cre)1Abel/?	involves: 129S4/SvJae * FVB	MGI:3029363
cn6	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Ckmm-cre)5Khn/?	involves: 129/Sv * C57BL/6	MGI:3029365

Genotype
MGI:3629925

cn1

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Myhca-cre)1Abel/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB

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

cardiovascular system

increased cardiac muscle glycogen level ( J:108830 )

• during normal perfusion, glycogen content is 54% higher in fed mutants than in fed wild-type, however no difference in myocardial glycogen in fasted mice

abnormal cardiovascular system physiology ( J:108830 )

• during normal perfusion, hearts from fed homozygotes show higher concentrations of phosphocreatine

decreased cardiac muscle cell glucose uptake ( J:108830 )

• during ischemia, hearts from fasted homozygotes exhibit depressed glucose utilization

increased cardiac muscle cell glucose uptake ( J:108830 )

• during normal perfusion, hearts from fed homozygotes show a 3-fold increase in glucose uptake, while fasted hearts show identical levels of basal glucose uptake as wild-type

decreased left ventricle systolic pressure ( J:108830 )

• fasting results in a 20% decrease in left ventricular systolic pressure, however heart rates and coronary flow rates are unaffected by fasting

abnormal response to cardiac infarction ( J:108830 )

• hearts exhibit delayed recovery after low-flow ischemia

• hearts of fasted mutants exhibit decreased lactate production (75%) indicating depressed glucose utilization during ischemia and develop irreversible systolic and diastolic dysfunction as indicated by an increase in left ventricular end-diastolic pressure that remains elevated on reperfusion and a left ventricular developed pressure that does not recovery fully, as well as impaired ability to generate ATP during ischemia (accelerated depletion of ATP and decreased levels of ATP recovery on reperfusion)

• hearts of fed mutants exhibit normal left ventricular pressure during ischemia, however recovery of the left ventricular developed pressure is delayed during reperfusion and hearts exhibit a decrease (28%) in lactate production during ischemia

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:108830 )

• during normal perfusion, glycogen content is 54% higher in fed mutants than in fed wild-type, however no difference in myocardial glycogen in fasted mice

abnormal response to cardiac infarction ( J:108830 )

• hearts exhibit delayed recovery after low-flow ischemia

• hearts of fasted mutants exhibit decreased lactate production (75%) indicating depressed glucose utilization during ischemia and develop irreversible systolic and diastolic dysfunction as indicated by an increase in left ventricular end-diastolic pressure that remains elevated on reperfusion and a left ventricular developed pressure that does not recovery fully, as well as impaired ability to generate ATP during ischemia (accelerated depletion of ATP and decreased levels of ATP recovery on reperfusion)

• hearts of fed mutants exhibit normal left ventricular pressure during ischemia, however recovery of the left ventricular developed pressure is delayed during reperfusion and hearts exhibit a decrease (28%) in lactate production during ischemia

muscle

increased cardiac muscle glycogen level ( J:108830 )

• during normal perfusion, glycogen content is 54% higher in fed mutants than in fed wild-type, however no difference in myocardial glycogen in fasted mice

decreased cardiac muscle cell glucose uptake ( J:108830 )

• during ischemia, hearts from fasted homozygotes exhibit depressed glucose utilization

increased cardiac muscle cell glucose uptake ( J:108830 )

• during normal perfusion, hearts from fed homozygotes show a 3-fold increase in glucose uptake, while fasted hearts show identical levels of basal glucose uptake as wild-type

cellular

decreased cardiac muscle cell glucose uptake ( J:108830 )

• during ischemia, hearts from fasted homozygotes exhibit depressed glucose utilization

increased cardiac muscle cell glucose uptake ( J:108830 )

• during normal perfusion, hearts from fed homozygotes show a 3-fold increase in glucose uptake, while fasted hearts show identical levels of basal glucose uptake as wild-type

Genotype
MGI:3663418

cn2

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4⁺; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * FVB

digestive/alimentary system

decreased intestinal glucose absorption ( J:110773 )

• insulin stimulated whole body uptake is decreased in heterozygous muscle-specific knockout mice

muscle

decreased muscle cell glucose uptake ( J:110773 )

• insulin stimulated muscle uptake is decreased in heterozygous muscle-specific knockout mice

cellular

decreased muscle cell glucose uptake ( J:110773 )

• insulin stimulated muscle uptake is decreased in heterozygous muscle-specific knockout mice

Genotype
MGI:3663416

cn3

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * FVB

homeostasis/metabolism

abnormal glucose homeostasis ( J:110773 )

• during a 2 hour hyperinsulinemic-euglycemic clamp insulin-stimulated whole body glycolysis is reduced by 59% (49 umol/kg/min vs 118 umol/kg/min in 21-week old controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated whole body glycolysis is reduced by 43% (95 umol/kg/min vs 166 umol/kg/min in young controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated skeletal muscle glycolysis is reduced by 92% (18 nmol/g/min vs 223 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, whole body glycolysis is reduced by 30% (98 vs 118 umol/kg/min) and and muscle glycolysis is reduced by 82% (44 vs 251 nmol/g/min); hepatic glucose production is unaffected by insulin

• during a 2 hour hyperinsulinemic-euglycemic clamp inhibition of hepatic glucose production by mutants is impaired in 21-week old mutants

increased circulating glucose level ( J:110773 )

• basal plasma glucose concentration (8.2mM) is increased about 20% compared to controls (Slc2a4^tm1Abel homozygotes at 21 weeks of age or mice expressing Tg(Ckmm-cre)1Khan alone) where levels are 6.8-7.2 mM

• however, young (0-week old) muscle-specific knockouts showed no increased plasma glucose vs age-matched controls

• in young mutants treated from 12 weeks of age with phloridzin, plasma glucose levels show an initial increase (10.2 vs 6.7 mM in controls) but levels gradually decrease to comparable levels with controls (8.2, 6.9 and 7.0 mM vs 7.0 mM in controls at 14, 17 and 20 weeks of age)

increased circulating insulin level ( J:110773 )

• 21-week old knockout mice do not show differences in basal plasma insulin levels after an overnight fast, while levels are significantly increased in young (10-week old) knockouts (~110 pM vs 53 pM) and phloridzin treated knockouts compared to their respective controls (166 pM vs 86 pM)

abnormal lipid homeostasis ( J:110773 )

• during a 2 hour hyperinsulinemic-euglycemic clamp insulin-stimulated whole body glycogen/lipid synthesis is decreased by 50% in 21-week old knockouts

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated whole body glycogen/lipid synthesis is decreased by 60% (36 vs 90 umol/kg/min) compared to young controls

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated skeletal muscle glycogen/lipid synthesis is decreased by 89% (0.7 vs 2.7 nmol/g/min) compared to young controls

• in young mutants treated from 12 weeks of age with phloridzin, whole body glycogen/lipid biosynthesis is decreased by 36% (44 vs 106 umol/kg/min) and muscle glycogen/lipid synthesis is reduced by 45% ( 4.7 vs 8.7 nmol/g/min)

muscle

decreased muscle cell glucose uptake ( J:110773 )

• uptake in skeletal (gastrocnemius) muscle is decreased by 92% in muscle-specific knockouts (20 vs 237 nmol/g/min in controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated uptake in skeletal muscle in 10-week old mutants is decreased by 85% (39 vs 261 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, skeletal muscle uptake is decreased by 81% (49 vs 227 nmol/g/min)

adipose tissue

decreased adipocyte glucose uptake ( J:110773 )

• insulin-stimulated glucose uptake in white adipose tissue and intracapsular brown adipose tissue is decreased by 69% (9 nmol/g/min vs 28 nmol/g/min) and 84% (37 nmol/g/min vs 237 nmol/g/min), respectively

increased adipocyte glucose uptake ( J:110773 )

• in 10 week old mutants insulin-stimulated uptake is increased 2-fold in white adipose tissue (26 vs 13 nmol/g/min) and brown adipose tissue (453 vs 224 nmol/g/min) compared to young controls

• in young mutants treated from 12 weeks of age with phloridzin, insulin-stimulated uptake in brown adipose tissue is increased (633 vs 247 nmol/g/min) but is unchanged in white adipose tissue

digestive/alimentary system

decreased intestinal glucose absorption ( J:110773 )

• in 21-week old mutants during a 2 hour hyperinsulinemic-euglycemic clamp insulin stimulated whole body uptake is decreased by 55% in muscle-specific knockout mice (102 umol/kg/min vs 224 umol/kg/min)

• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated whole body uptake in 10-week old mutants is decreased by 49% (130 vs 256 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, whole body uptake is decreased by 32% (142 vs 224 umol/kg/min)

cellular

decreased adipocyte glucose uptake ( J:110773 )

• insulin-stimulated glucose uptake in white adipose tissue and intracapsular brown adipose tissue is decreased by 69% (9 nmol/g/min vs 28 nmol/g/min) and 84% (37 nmol/g/min vs 237 nmol/g/min), respectively

increased adipocyte glucose uptake ( J:110773 )

• in 10 week old mutants insulin-stimulated uptake is increased 2-fold in white adipose tissue (26 vs 13 nmol/g/min) and brown adipose tissue (453 vs 224 nmol/g/min) compared to young controls

• in young mutants treated from 12 weeks of age with phloridzin, insulin-stimulated uptake in brown adipose tissue is increased (633 vs 247 nmol/g/min) but is unchanged in white adipose tissue

decreased muscle cell glucose uptake ( J:110773 )

• uptake in skeletal (gastrocnemius) muscle is decreased by 92% in muscle-specific knockouts (20 vs 237 nmol/g/min in controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated uptake in skeletal muscle in 10-week old mutants is decreased by 85% (39 vs 261 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, skeletal muscle uptake is decreased by 81% (49 vs 227 nmol/g/min)

Genotype
MGI:3029364

cn4

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Fabp4-cre)1Abel/?
• Genetic Background: involves: 129S4/SvJae * FVB

homeostasis/metabolism

abnormal glucose homeostasis ( J:67292 )

• basal glucose uptake reduced about 40% in adipocytes

• insulin mediated glucose uptake was blunted to a maximum of about 72%

• whole body glucose uptake reduced 53%

• glycolysis down 50%

• transport in to white and brown adipose tissue and skeletal muscle reduced

• insulin unable to suppress hepatic glucose production

abnormal glucose tolerance ( J:67292 )

• impaired glucose tolerance as early as 13 weeks and persisting until after 31 weeks of age

abnormal glycogen homeostasis ( J:67292 )

• glycogen synthesis down 67%

insulin resistance ( J:67292 )

• as early as 12 weeks and sometimes becomes extreme

Genotype
MGI:3029363

cn5

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Myhca-cre)1Abel/?
• Genetic Background: involves: 129S4/SvJae * FVB

cardiovascular system

abnormal heart morphology ( J:59054 )

abnormal myocardium layer morphology ( J:59054 )

• cross sectional area of myocytes was greater

• gross morphology of the heart was normal however

increased heart weight ( J:59054 )

• both heart weight and heart wt/body wt ratio were significantly increased

cardiac hypertrophy ( J:59054 )

• develop cardiac hypertrophy, however contractile function is preserved

abnormal cardiovascular system physiology ( J:59054 )

• increased ANP production

decreased cardiac muscle cell glucose uptake ( J:59054 )

• insulin mediated glucose uptake was abolished in the heart

growth/size/body

increased heart weight ( J:59054 )

• both heart weight and heart wt/body wt ratio were significantly increased

cardiac hypertrophy ( J:59054 )

• develop cardiac hypertrophy, however contractile function is preserved

decreased body weight ( J:59054 )

• growth was normal up to about 6 months

• body weight in older males was reduced relative to wild-type males

homeostasis/metabolism

abnormal glucose homeostasis ( J:59054 )

• basal glucose uptake about 4X normal in males and 2X normal in females

• insulin mediated glucose uptake was abolished in the heart

abnormal glucose tolerance ( J:59054 )

• glucose tolerance was normal until about 30 weeks of age when mild impairment was seen in females

muscle

abnormal myocardium layer morphology ( J:59054 )

• cross sectional area of myocytes was greater

• gross morphology of the heart was normal however

decreased cardiac muscle cell glucose uptake ( J:59054 )

• insulin mediated glucose uptake was abolished in the heart

nervous system

abnormal nervous system physiology ( J:59054 )

• increased BNP production

cellular

decreased cardiac muscle cell glucose uptake ( J:59054 )

• insulin mediated glucose uptake was abolished in the heart

Genotype
MGI:3029365

cn6

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129/Sv * C57BL/6

growth/size/body

decreased body weight ( J:75418 )

• growth was normal up to about 6 months

• weight gain became slower in older animals

• heart weight to body weight ratio increased 55% by 10 weeks of age

homeostasis/metabolism

abnormal circulating glucose level ( J:75418 )

• fasting and fed blood glucose levels increased from 2 to 4 months and then plateaued

hyperglycemia ( J:75418 )

• at 4 months both fed and fasted mice were hyperglycemic

abnormal glucose tolerance ( J:75418 )

• impaired glucose tolerance by 2 months and progressed until 4 months

increased liver glycogen level ( J:75418 )

• liver glycogen levels up 450%, comparable to increase in glucose uptake by liver

insulin resistance ( J:75418 )

• as early as 8 weeks in muscle

• glucose levels did not decrease in males in response to insulin injection and decreased by 34% in females

abnormal lipid homeostasis ( J:75418 )

abnormal lipid level ( J:75418 )

• cholesterol and free faty acid levels normal to 6 months of age

decreased fatty acids level ( J:75418 )

• fasting beta-hydroxybuterate levels lowered

decreased triglyceride level ( J:75418 )

muscle

muscle phenotype ( J:75418 )

N • muscle mass was normal

abnormal muscle physiology ( J:75418 )

• lactate levels in muscles of male mice were reduced

decreased muscle cell glucose uptake ( J:75418 )

• basal glucose uptake reduced 73-88% in skeletal muscle

• insulin and contraction both fail to stimulate glucose transport

liver/biliary system

increased liver glycogen level ( J:75418 )

• liver glycogen levels up 450%, comparable to increase in glucose uptake by liver

cellular

decreased muscle cell glucose uptake ( J:75418 )

• basal glucose uptake reduced 73-88% in skeletal muscle

• insulin and contraction both fail to stimulate glucose transport