Mouse Genome Informatics
hm1
    Kcnj11tm1Sse/Kcnj11tm1Sse
B6.129P2-Kcnj11tm1Sse
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• body weight is lower than controls after 20 weeks on a regular diet
• resistant to obesity on a high fat diet

homeostasis/metabolism
• reduced capacity relative to controls
• unable to sustain the same level of performance as controls for as long a period of time
• after 60 minutes of volume expansion, the plasma ANF level in knockouts increases significantly, whereas in wild-type there is no change
• higher rate of caloric output
• cumulative carbohydrate utilization in a 12 hour period is 4.5-5g/kg higher than in controls
• resistant to obesity on a high fat diet
• higher oxygen consumption under sedentary conditions
• 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
• severely impaired recovery from systemic hypoglycemia caused by insulin injection

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

nervous system
• after 5 minutes of stretch, the action potential duration in the atria of knockouts remains unaltered but in wild-type it is shortened
• ventromedial hypothalamus neurons display higher discharge rates at low glucose levels which fail to increase at higher glucose levels

behavior/neurological
• 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)
• duration of voluntary activity is about half that of controls although the number of activity bouts is about the same
• reduced capacity relative to controls
• unable to sustain the same level of performance as controls for as long a period of time

adipose tissue
• depletion of subcutaneous fat deposits by 1 year of age
• depletion of abdominal fat deposits by 1 year of age

endocrine/exocrine glands
• 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
• depletion of subcutaneous fat deposits by 1 year of age

pigmentation
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 Oct2p and/or Tyrc-ch were inherited from the ESCell line used to generate the targeted allele Kcnj11tm1Sse (J:157001)


Mouse Genome Informatics
hm2
    Kcnj11tm1Sse/Kcnj11tm1Sse
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in response to elevated glucose levels or glucose and tolbutamide, insulin secretion by mutant beta cells is impaired compared to wild-type beta cells
• glucose tolerance in homozygous knockouts is slightly impaired compared to wild-type
• imutants injected with low doses of insulin display a significant lowering of blood glucose levels compared to wild-type

nervous system
• myoclonic jerk in response to 150 seconds of hypoxia
• severe tonic-clonic convulsion and death after hypoxia induced myoclonic jerk
• firing rate of substantia nigra pars reticulata neurons increases about 1.8 fold during hypoxia rather than decreasing as it does in controls
• substantia nigra pars reticulata neurons depolarize rather than hyperpolarize in hypoxic media

muscle
• myoclonic jerk in response to 150 seconds of hypoxia
• 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)
• 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
• peak tetanic force during fatigue initially drops faster than in controls although it is similar to controls after 90 seconds

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

behavior/neurological
• myoclonic jerk in response to 150 seconds of hypoxia
• severe tonic-clonic convulsion and death after hypoxia induced myoclonic jerk


Mouse Genome Informatics
hm3
    Kcnj11tm1Sse/Kcnj11tm1Sse
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• spend more time on open and less in closed arms of an elevated plus maze than do controls
• 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
• females are less active than controls in spontaneous exploration tests
• lower rate of alternation in a spontaneous alternation test
• 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
• significantly more home cage activity than controls
• less active than controls in open field tests, fewer squares crossed
• less rearing and longer latency to first rearing


Mouse Genome Informatics
cx4
    Kcnj11tm1Sse/Kcnj11+
Tg(Ins1-Kcnj11*)#Nich/?

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• reduced glucose stimulated insulin on a high fat diet
• elevated glucose stimulated insulin secretion at 4 months of age
• higher blood glucose on a high fat diet
• elevated plasma insulin relative to controls on a normal diet but not on a high fat diet
• glucose intolerant on a high fat diet
• enhanced glucose tolerance at 4 months of age

endocrine/exocrine glands
• higher insulin content in islets on a normal diet
• normal insulin content in islets on a high fat diet
• reduced glucose stimulated insulin on a high fat diet
• elevated glucose stimulated insulin secretion at 4 months of age


Mouse Genome Informatics
cx5
    Kcnj11tm1Sse/Kcnj11tm1Sse
Tg(Ins1-Kcnj11*)#Nich/?

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• plasma insulin is not elevated on a high fat diet (J:94610)
• reduced baseline insulin secretion but normal plasma insulin
• on a normal diet
• significantly increased blood glucose on a high fat diet relative to controls
• decreased glucose tolerance on both normal and high fat diet

endocrine/exocrine glands
• reduced baseline insulin secretion but normal plasma insulin