Phenotypes associated with this allele

• Allele Symbol: Tg(GFAP-cre)1Kdmc
• Allele Name: transgene insertion 1, Ken D McCarthy
• Allele ID: MGI:3655847
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Kcnj10^tm1Kdmc/Kcnj10^tm1Kdmc Tg(GFAP-cre)1Kdmc/?	involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J * SJL	MGI:3761721
cn2	Gja1^tm1Dlg/Gja1^tm1Dlg Tg(GFAP-cre)1Kdmc/0	involves: 129S7/SvEvBrd * C3H * C57BL/6 * C57BL/6J	MGI:4420313

Genotype
MGI:3761721

cn1

• 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

Genotype
MGI:4420313

cn2

• Allelic Composition: Gja1^tm1Dlg/Gja1^tm1Dlg; Tg(GFAP-cre)1Kdmc/0
• Genetic Background: involves: 129S7/SvEvBrd * C3H * C57BL/6 * C57BL/6J

mortality/aging

premature death ( J:156098 )

• Shuffler mice develop motor defects and die apparently due to malnutrition

nervous system

abnormal radial glial cell morphology ( J:156098 )

• at P2, radial glial cells in Shuffler mice that stretch across the cortical layers are not as prominent or organized as in wild-type mice

abnormal brain morphology ( J:156098 )

• Background Sensitivity: mice further backcrossed to 129S/SvEv exhibit behavioral and neurological defects identified as the Shuffler phenotype unlike mice further backcrossed to C57BL/6J mice

• the relationship between the mesencephalon and the dorsal telencephalon is altered in Shuffler mice compared to in wild-type mice

abnormal cortical ventricular zone morphology ( J:156098 )

• at P2, the Shuffler ventricular zone is virtually cell-free, particularly in the lateral and medial cortex, unlike in wild-type mice

• however, the ventricular zone is normal at P10

enlarged brain ventricles ( J:156098 )

• Shuffler mice exhibit enlarged ventricles compared with wild-type mice

enlarged lateral ventricles ( J:156098 )

• sporadically in Shuffler mice

abnormal hippocampus morphology ( J:156098 )

• at P10, neuronal lamination and size of the hippocampus and cerebellum in Shuffler mice progressively deteriorate compared to in wild-type mice

• Shuffler mice exhibit disorganized neuronal lamination with abnormal dispersal of the CA3 field compared to in wild-type mice

abnormal dentate gyrus morphology ( J:156098 )

• the suprapyramidal blade of the dentate gyrus in the rostral and medial portions of most Shuffler hippocampus is missing unlike in wild-type mice

small hippocampus ( J:156098 )

• in most Shuffler mice at P2 and P60, especially caudally

abnormal cerebellum morphology ( J:156098 )

• at P10, neuronal lamination and size of the hippocampus and cerebellum in Shuffler mice progressively deteriorate compared to in wild-type mice

• at P60, Shuffler mice exhibit a disorganized cerebellum unlike in wild-type mice

• Shuffler mice exhibit abnormal lamination of the cerebellum unlike wild-type mice

• mildly affected Shuffler mice exhibit abnormalities throughout the entire cerebellum while severely affected Shuffler mice exhibit defects in the rostral cerebellar lobes

abnormal cerebellum external granule cell layer morphology ( J:156098 )

• contains ectopic masses composed of neuronal and glial cells in Shuffler mice

thin external granule cell layer ( J:156098 )

• in Shuffler mice at P2, but not P10

abnormal cerebellar cortex morphology ( J:156098 )

• at P2, the cerebellar cortex of Shuffler mice exhibits cell loss and disorganization compared to in wild-type mice

• at P60, the cerebellar cortex is thin in Shuffler mice compared to in wild-type mice

• Shuffler mice exhibit delamination and disorganization of Purkinje cells, granule cells, and Bergmann glia compared with wild-type mice

• Shuffler mice exhibit disrupted Bergmann glia morphology and lamination compared with wild-type mice

• however, cortical lamination is normal at P10

abnormal cerebellar lobule formation ( J:156098 )

• severely affected Shuffler mice exhibit fused lobes unlike in wild-type mice

abnormal cerebellar Purkinje cell layer ( J:156098 )

• Purkinje cells in Shuffler mice are dispersed and less organized than in wild-type mice

delaminated Purkinje cell layer ( J:156098 )

• in Shuffler mice

abnormal cerebellar granule layer morphology ( J:156098 )

• disorganized in Shuffler mice

ectopic cerebellar granule cells ( J:156098 )

• in some Shuffler mice

delaminated cerebellar granule layer ( J:156098 )

• in Shuffler mice

small cerebellum ( J:156098 )

• in Shuffler mice at P2 and P10

abnormal postnatal subventricular zone morphology ( J:156098 )

• at P2, the subventricular zone of Shuffler mice accumulates cells unlike in wild-type mice

• however, the subventricular zone is normal at P10

behavior/neurological

abnormal behavior ( J:156098 )

• Background Sensitivity: mice further backcrossed to 129S/SvEv exhibit behavioral and neurological defects identified as the Shuffler phenotype unlike mice further backcrossed to C57BL/6J mice

poor grooming ( J:156098 )

• at weaning but not at later time points

abnormal motor capabilities/coordination/movement ( J:156098 )

• Shuffler mice develop motor defects and die apparently due to malnutrition

ataxia ( J:156098 )

• in Shuffler mice

abnormal gait ( J:156098 )

• in Shuffler mice

growth/size/body

decreased body size ( J:156098 )

• at weaning but not at later time points

cellular

abnormal radial glial cell morphology ( J:156098 )

• at P2, radial glial cells in Shuffler mice that stretch across the cortical layers are not as prominent or organized as in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oculodentodigital dysplasia		DOID:0060291	OMIM:164200 OMIM:257850	J:156098