Phenotypes associated with this allele

• Allele Symbol: Arx^tm4Kki
• Allele Name: targeted mutation 4, Kunio Kitamura
• Allele ID: MGI:4359177
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ot1	Arx^tm4Kki/Y	involves: 129S/SvEv * C57BL/6J	MGI:4359207
ot2	Arx^tm4Kki/Y	involves: 129S/SvEv * C57BL/6NHsd	MGI:6196032

Genotype
MGI:4359207

ot1

• Allelic Composition: Arx^tm4Kki/Y
• Genetic Background: involves: 129S/SvEv * C57BL/6J

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

mortality/aging

premature death ( J:152416 )

♂ • most mice die within 3 months with some surviving for 5 to 6 months

nervous system

seizures ( J:152416 )

♂ • by 1 month, 7 of 10 mice exhibit seizures with one death during status epilepticus

♂ • some mice exhibit hand-washing motion at the end of a seizure

tonic seizures ( J:152416 )

♂

abnormal spike wave discharge ( J:152416 )

♂ • mice exhibit abnormal activities during ictal electroencephalogram with positive spikes in the hippocampus and negative spikes in the frontal cortex and striatum followed by diffuse spike bursts

abnormal neuronal migration ( J:152416 )

♂ • 88% of Arx+ GABAergic cells that migrate in wild-type mice reach the cortical plate by P0

♂ • at P0, tangential migration of SST+ GABAergic neurons is suppressed compared to in wild-type mice

loss of GABAergic neurons ( J:152416 )

♂ • severe in the cortex and striatum

abnormal cholinergic neuron morphology ( J:152416 )

♂ • at 1 month, cholinergic neurons in the striatum, medial septum, and ventral forebrain nuclei are reduced compared to in wild-type mice

behavior/neurological

impaired passive avoidance behavior ( J:152416 )

♂ • compared to wild-type mice that is worse than in Arx^tm3Kki homozygotes

abnormal spatial learning ( J:152416 )

♂ • mice exhibit impaired spatial learning in a win-shift task on the 8-arm radial maze compared with wild-type mice that is worse than in Arx^tm3Kki homozygotes

♂ • in a win-stay task, mice exhibit higher unlit-to-lit ratio throughout training compared with wild-type mice

♂ • abnormal spatial learning is independent of hyperactivity and anxiety-like behaviors

increased anxiety-related response ( J:152416 )

♂

impaired coordination ( J:152416 )

♂

hyperactivity ( J:152416 )

♂

seizures ( J:152416 )

♂ • by 1 month, 7 of 10 mice exhibit seizures with one death during status epilepticus

♂ • some mice exhibit hand-washing motion at the end of a seizure

tonic seizures ( J:152416 )

♂

abnormal spike wave discharge ( J:152416 )

♂ • mice exhibit abnormal activities during ictal electroencephalogram with positive spikes in the hippocampus and negative spikes in the frontal cortex and striatum followed by diffuse spike bursts

cellular

abnormal neuronal migration ( J:152416 )

♂ • 88% of Arx+ GABAergic cells that migrate in wild-type mice reach the cortical plate by P0

♂ • at P0, tangential migration of SST+ GABAergic neurons is suppressed compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
early infantile epileptic encephalopathy		DOID:0050709		J:197588

Genotype
MGI:6196032

ot2

• Allelic Composition: Arx^tm4Kki/Y
• Genetic Background: involves: 129S/SvEv * C57BL/6NHsd

mortality/aging

premature death ( J:260340 )

♂ • 55% of mice survive to P70

postnatal lethality, incomplete penetrance ( J:260340 )

♂ • first death occurs at P19, with only 86% of mice being successfully weaned, and with 55% surviving to P70

growth/size/body

decreased body weight ( J:260340 )

♂ • lower body weight throughout development and growth, with weight fluctuations often seen pre- and post-seizure

♂ • mice weight 83% of control at P5, 73% of control at weaning, and 80-90% of control between P35 and P70

behavior/neurological

decreased exploration in new environment ( J:260340 )

♂ • mice travel less total distance and spend less time in the inner quadrants of the open field, suggesting decreased exploratory behavior

increased exploration in new environment ( J:260340 )

♂ • mice travel greater distance and spend more time on the open arm of the elevated zero maze indicating increased exploratory behavior

impaired spatial learning ( J:260340 )

♂ • mice exhibit reduced spatial learning and memory in the Y-maze and Barnes maze, showing no preference for the novel arm in the Y-maze, an increase in time to locate the escape hole in the Barns maze and no preference towards the previously learned (familiar) or rotated (novel) location of the escape hole

increased anxiety-related response ( J:260340 )

♂ • mice travel less total distance and spend less time in the inner quadrants of the open field, suggesting increased anxiety

decreased fear-related response ( J:260340 )

♂ • mice exhibit decreased fear response in the elevated zero maze, traveling a greater distance and spending more time in the open arm

abnormal motor capabilities/coordination/movement ( J:260340 )

♂ • 32% of mice show one or more movement phenotypes (such as jumpy or erratic movements when handled or provoked, rapid uncontrolled movement around the cage, twitching ears, straight tail, or increased facial grooming), either singularly or in combination with a myoclonic seizure at 1 month of age which progresses to 91% of mice at P70

decreased locomotor activity ( J:260340 )

♂ • mice show reduced locomotor activity in the open field

abnormal social investigation ( J:260340 )

♂ • mice show reduced sociability and social novelty, showing reduced interaction time within the chamber, regardless of the occupant

abnormal response to social novelty ( J:260340 )

♂ • mice show reduced social novelty, showing reduced interaction time with the novel mouse

social withdrawal ( J:260340 )

♂ • any interaction with a stranger or familiar mouse is at a greater distance

myoclonus ( J:260340 )

♂ • first myoclonic seizures are seen at P18 during handling of mice

♂ • by P21, 18% of mice exhibit myoclonic seizures

♂ • by P70, 73% of mice exhibit spontaneous seizures

muscle

myoclonus ( J:260340 )

♂ • first myoclonic seizures are seen at P18 during handling of mice

♂ • by P21, 18% of mice exhibit myoclonic seizures

♂ • by P70, 73% of mice exhibit spontaneous seizures

nervous system

myoclonus ( J:260340 )

♂ • first myoclonic seizures are seen at P18 during handling of mice

♂ • by P21, 18% of mice exhibit myoclonic seizures

♂ • by P70, 73% of mice exhibit spontaneous seizures

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
early infantile epileptic encephalopathy		DOID:0050709		J:260340