Phenotypes Associated with This Genotype

Genotype
MGI:3761721

• Allelic Composition: Kcnj10^tm1Kdmc/Kcnj10^tm1Kdmc; Tg(GFAP-cre)1Kdmc/?
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J * SJL

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

mortality/aging

premature death ( J:126082 )

• all mice are dead by 30 days after birth

nervous system

abnormal nervous system morphology ( J:126082 )

decreased brain size ( J:126082 )

dilated lateral ventricle ( J:126082 )

thin cerebral cortex ( J:126082 )

brain vacuoles ( J:126082 )

• vacuolization in the brain and spinal cord is observed and is most notable in the cerebellar internal capsule, corpus callosum, thalamus and spinal cord white matter

abnormal CNS glial cell morphology ( J:126082 )

• glial cells that exhibit complex electrophysiological profiles are rarely found in mice and there is an 11-fold reduction in the number of complex glial cells at P5 to P10 and 9-fold at P11 to P15 compared to in wild-type mice

• unlike in wild-type mice, complex glial cells are never found in stratum radiatum of P16 to P20 or P21 to P30 mice

• complex glial cells are markedly depolarized compared to in wild-type mice and exhibit a 4.1-fold increase in membrane resistance

abnormal astrocyte morphology ( J:126082 )

• mice exhibit a 2.4-fold increase in membrane resistance and a decrease in the size of whole-cell current in passive glial cells

• however, passive glial cells do not preferentially loose inward current and glial cell morphology and gap junction coupling are normal

abnormal oligodendrocyte morphology ( J:126082 )

• membrane depolarization is observed in mature myelinating oligodendrocytes in the corpus callosum

gliosis ( J:126082 )

• most evident in transverse spinal cord sections

abnormal spinal cord white matter morphology ( J:126082 )

• vacuolization in the brain and spinal cord is observed and is most notable in the cerebellar internal capsule, corpus callosum, thalamus and spinal cord white matter

abnormal nervous system physiology ( J:126082 )

tonic-clonic seizures ( J:126082 )

• when stimulated by sudden movement mice exhibit grand mal seizures with hyperextension of the back and limb rigidity

• mice recover from seizures within 30 seconds

abnormal astrocyte physiology ( J:126082 )

• potassium and glutamate uptake by passive astrocytes is severely impaired compared to in wild-type cells

abnormal CNS synaptic transmission ( J:126082 )

• short term potential is 19% greater than in wild-type mice

abnormal excitatory postsynaptic currents ( J:126082 )

• spontaneous excitatory postsynaptic currents in CA1 pyramidal neuron frequency and peak amplitude compared to wild-type mice

enhanced long-term potentiation ( J:126082 )

• long term potentiation is enhanced compared to in wild-type mice for the first 20 minutes after stimulation

• long term potentiation 30 to 45 minutes after stimulation is increased (133.1+/-5.1% compared to 126.0+/-3.2% in wild-type mice)

increased post-tetanic potentiation ( J:126082 )

• post-tetanic potential is 30% greater than in wild-type mice

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:126082 )

• mice can not climb or suspend themselves from the cage bars preventing additional behavioral testing

lethargy ( J:126082 )

• develops over time

impaired righting response ( J:126082 )

tremors ( J:126082 )

• develops over time

ataxia ( J:126082 )

• over time mice develop ataxia with frequent falls to the side

hindlimb paralysis ( J:126082 )

• hindlimb paralysis and splaying are frequently observed

tonic-clonic seizures ( J:126082 )

• when stimulated by sudden movement mice exhibit grand mal seizures with hyperextension of the back and limb rigidity

• mice recover from seizures within 30 seconds

vision/eye

delayed eyelid opening ( J:126082 )

• mice exhibit visual deficiencies attributed to complete or partial eye closure

eyelids fail to open ( J:126082 )

• mice exhibit visual deficiencies attributed to complete or partial eye closure

abnormal eye physiology ( J:126082 )

• mice exhibit visual deficiencies attributed to complete or partial eye closure

growth/size/body

decreased body size ( J:126082 )

• at P12 to P15, mice begin to appear runted

slow postnatal weight gain ( J:126082 )

• mice stop gaining weight at P15 after reaching 5 to 6 g in weight