Phenotypes associated with this allele

• Allele Symbol: Kcnj11^tm1Sse
• Allele Name: targeted mutation 1, Susumu Seino
• Allele ID: MGI:2178821
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kcnj11^tm1Sse/Kcnj11^tm1Sse	B6.129P2-Kcnj11^tm1Sse	MGI:3619147
hm2	Kcnj11^tm1Sse/Kcnj11^tm1Sse	involves: 129P2/OlaHsd	MGI:3619152
hm3	Kcnj11^tm1Sse/Kcnj11^tm1Sse	involves: 129P2/OlaHsd * C57BL/6	MGI:5432915
cx4	Kcnj11^tm1Sse/Kcnj11^+ Tg(Ins1-Kcnj11*)#Nich/?	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5432921
cx5	Kcnj11^tm1Sse/Kcnj11^tm1Sse Tg(Ins1-Kcnj11*)#Nich/?	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5432923

Genotype
MGI:3619147

hm1

• Allelic Composition: Kcnj11^tm1Sse/Kcnj11^tm1Sse
• Genetic Background: B6.129P2-Kcnj11^tm1Sse

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

growth/size/body

slow postnatal weight gain ( J:157001 )

• body weight is lower than controls after 20 weeks on a regular diet

decreased susceptibility to diet-induced obesity ( J:157001 )

• resistant to obesity on a high fat diet

homeostasis/metabolism

decreased aerobic running capacity ( J:157001 )

• reduced capacity relative to controls

• unable to sustain the same level of performance as controls for as long a period of time

increased circulating atrial natriuretic factor ( J:106396 )

• after 60 minutes of volume expansion, the plasma ANF level in knockouts increases significantly, whereas in wild-type there is no change

increased energy expenditure ( J:157001 )

• higher rate of caloric output

• cumulative carbohydrate utilization in a 12 hour period is 4.5-5g/kg higher than in controls

decreased susceptibility to diet-induced obesity ( J:157001 )

• resistant to obesity on a high fat diet

increased oxygen consumption ( J:157001 )

• higher oxygen consumption under sedentary conditions

abnormal glucose homeostasis ( J:69163 )

decreased glucagon secretion ( J:69163 )

• significantly reduced although glucose secretion of isolated alpha-cells is normal

• injection of 2-deoxyglucose into the 3rd ventricle fails to stimulate glucagon secretion as it does in controls

hypoglycemia ( J:69163 )

• severely impaired recovery from systemic hypoglycemia caused by insulin injection

cardiovascular system

increased mean systemic arterial blood pressure ( J:106396 )

• after 60 minutes of volume expansion in knockouts, there is a significant increase in mean arterial pressure compared to wild-type

nervous system

abnormal action potential ( J:106396 )

• after 5 minutes of stretch, the action potential duration in the atria of knockouts remains unaltered but in wild-type it is shortened

abnormal nerve fiber response ( J:69163 )

• ventromedial hypothalamus neurons display higher discharge rates at low glucose levels which fail to increase at higher glucose levels

behavior/neurological

abnormal food intake ( J:69163 , J:157001 )

• food intake is stimulated less by 2-deoxyglucose injection than is true in controls (J:69163)

• elevated intake of food at 3-4 months of age (J:157001)

abnormal locomotor activation ( J:157001 )

• duration of voluntary activity is about half that of controls although the number of activity bouts is about the same

decreased aerobic running capacity ( J:157001 )

• reduced capacity relative to controls

• unable to sustain the same level of performance as controls for as long a period of time

adipose tissue

decreased subcutaneous adipose tissue amount ( J:157001 )

• depletion of subcutaneous fat deposits by 1 year of age

decreased abdominal fat pad weight ( J:157001 )

• depletion of abdominal fat deposits by 1 year of age

endocrine/exocrine glands

decreased glucagon secretion ( J:69163 )

• significantly reduced although glucose secretion of isolated alpha-cells is normal

• injection of 2-deoxyglucose into the 3rd ventricle fails to stimulate glucagon secretion as it does in controls

integument

decreased subcutaneous adipose tissue amount ( J:157001 )

• depletion of subcutaneous fat deposits by 1 year of age

pigmentation

pigmentation phenotype ( J:157001 )

N • authors note that mutant mice are white rather than non-agouti black as expected on this congenic background and suggest that the non-B6 coat colors Oct2^p and/or Tyr^c-ch were inherited from the ESCell line used to generate the targeted allele Kcnj11^tm1Sse

Genotype
MGI:3619152

hm2

• Allelic Composition: Kcnj11^tm1Sse/Kcnj11^tm1Sse
• Genetic Background: involves: 129P2/OlaHsd

homeostasis/metabolism

decreased circulating insulin level ( J:49755 )

• in response to elevated glucose levels or glucose and tolbutamide, insulin secretion by mutant beta cells is impaired compared to wild-type beta cells

impaired glucose tolerance ( J:49755 )

• glucose tolerance in homozygous knockouts is slightly impaired compared to wild-type

increased insulin sensitivity ( J:49755 )

• imutants injected with low doses of insulin display a significant lowering of blood glucose levels compared to wild-type

nervous system

convulsive seizures ( J:69832 )

myoclonus ( J:69832 )

• myoclonic jerk in response to 150 seconds of hypoxia

tonic-clonic seizures ( J:69832 )

• severe tonic-clonic convulsion and death after hypoxia induced myoclonic jerk

abnormal nerve fiber response ( J:69832 )

• firing rate of substantia nigra pars reticulata neurons increases about 1.8 fold during hypoxia rather than decreasing as it does in controls

abnormal nerve fiber response intensity ( J:69832 )

• substantia nigra pars reticulata neurons depolarize rather than hyperpolarize in hypoxic media

muscle

myoclonus ( J:69832 )

• myoclonic jerk in response to 150 seconds of hypoxia

impaired skeletal muscle contractility ( J:105244 , J:140833 )

• tetanic force and maximum rate of force development reduced by 24-40% compared to younger mice as to a 7-17% reduction in controls (J:105244)

• tetanic force and maximum rate of force development is 21-23% less than in control mice (J:105244)

• recovery of tetanic force in 1 year old mice is considerable less than for controls (J:105244)

• mean peak tetanic force in the flexor digitorum brevis is significantly less than for controls (J:140833)

• peak total tetanic force drops faster than in controls for 30 seconds but then is significantly greater than in controls (J:140833)

• peak tetanic force recovery after fatigue is significantly slower than in controls (J:140833)

abnormal muscle relaxation ( J:105244 )

• half relaxation times are similar at 1 year and at 2-3 months whereas these times are considerably slower in 1 year old controls than in 2-3 month old controls

• resting tensions of extensor digitorum longus muscle from 2-3 month old mice are 5.6% of prefatigue tetanic force compared to 1.6-2.2% for controls

• resting tensions of 1 year old mice are 8.7% of prefatigue tetanic force

increased muscle fatigability ( J:140833 )

• peak tetanic force during fatigue initially drops faster than in controls although it is similar to controls after 90 seconds

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:69832 )

• severe tonic-clonic convulsion and death after hypoxia induced myoclonic jerk

behavior/neurological

convulsive seizures ( J:69832 )

myoclonus ( J:69832 )

• myoclonic jerk in response to 150 seconds of hypoxia

tonic-clonic seizures ( J:69832 )

• severe tonic-clonic convulsion and death after hypoxia induced myoclonic jerk

Genotype
MGI:5432915

hm3

• Allelic Composition: Kcnj11^tm1Sse/Kcnj11^tm1Sse
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

behavior/neurological

abnormal spatial reference memory ( J:112822 )

• lower rate of alternation in a spontaneous alternation test

abnormal emotion/affect behavior ( J:112822 )

decreased exploration in new environment ( J:112822 )

• females are less active than controls in spontaneous exploration tests

decreased anxiety-related response ( J:112822 )

• spend more time on open and less in closed arms of an elevated plus maze than do controls

increased anxiety-related response ( J:112822 )

• spend most or all of their time in the fully enclosed alley of a successive alley test

• males but not females are considerably slower to drink in a hyponeophagia test than controls

• hyponeophagia results for males are reversed in a second test

abnormal motor capabilities/coordination/movement ( J:112822 )

impaired coordination ( J:112822 )

• markedly impaired performance on a static rod test

• slower to reorient themselves and move to safety

• more likely to fall off the rod

• normal rotarod performance

• slight impairment of performance on a horizontal bar test

abnormal locomotor activation ( J:112822 )

• significantly more home cage activity than controls

• less active than controls in open field tests, fewer squares crossed

decreased vertical activity ( J:112822 )

• less rearing and longer latency to first rearing

Genotype
MGI:5432921

cx4

• Allelic Composition: Kcnj11^tm1Sse/Kcnj11⁺; Tg(Ins1-Kcnj11*)#Nich/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

homeostasis/metabolism

decreased insulin secretion ( J:94610 )

• reduced glucose stimulated insulin on a high fat diet

increased insulin secretion ( J:94610 )

• elevated glucose stimulated insulin secretion at 4 months of age

increased circulating glucose level ( J:94610 )

• higher blood glucose on a high fat diet

increased circulating insulin level ( J:94610 )

• elevated plasma insulin relative to controls on a normal diet but not on a high fat diet

impaired glucose tolerance ( J:94610 )

• glucose intolerant on a high fat diet

improved glucose tolerance ( J:94610 )

• enhanced glucose tolerance at 4 months of age

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:94610 )

• higher insulin content in islets on a normal diet

• normal insulin content in islets on a high fat diet

decreased insulin secretion ( J:94610 )

• reduced glucose stimulated insulin on a high fat diet

increased insulin secretion ( J:94610 )

• elevated glucose stimulated insulin secretion at 4 months of age

Genotype
MGI:5432923

cx5

• Allelic Composition: Kcnj11^tm1Sse/Kcnj11^tm1Sse; Tg(Ins1-Kcnj11*)#Nich/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:94610 )

N • plasma insulin is not elevated on a high fat diet

decreased insulin secretion ( J:94610 )

• reduced baseline insulin secretion but normal plasma insulin

increased circulating glucose level ( J:94610 )

• on a normal diet

• significantly increased blood glucose on a high fat diet relative to controls

impaired glucose tolerance ( J:94610 )

• decreased glucose tolerance on both normal and high fat diet

endocrine/exocrine glands

decreased insulin secretion ( J:94610 )

• reduced baseline insulin secretion but normal plasma insulin