Phenotypes associated with this allele

• Allele Symbol: Arx^tm1.1Jno
• Allele Name: targeted mutation 1.1, Jeffrey L Noebels
• Allele ID: MGI:4353222
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arx^tm1.1Jno/Arx^tm1.1Jno	involves: 129S7/SvEvBrd * C57BL/6J	MGI:4353224
ot2	Arx^tm1.1Jno/Y	involves: 129S7/SvEvBrd * C57BL/6J	MGI:4353223

Genotype
MGI:4353224

hm1

• Allelic Composition: Arx^tm1.1Jno/Arx^tm1.1Jno
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

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

behavior/neurological

myoclonus ( J:151082 )

♀ • at P7 the incidence of high amplitude movements including sustained spasm-like movements strong enough to cause the pup to flip over, axial contractions that bow or twist the body, and abrupt lateral displacements, is increased

♀ • the frequency of these high amplitude movements decreases between P9 and P11

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:151082 )

♀N • unlike null mice, no abnormalities in pancreatic morphology or physiology are detected

muscle

myoclonus ( J:151082 )

♀ • at P7 the incidence of high amplitude movements including sustained spasm-like movements strong enough to cause the pup to flip over, axial contractions that bow or twist the body, and abrupt lateral displacements, is increased

♀ • the frequency of these high amplitude movements decreases between P9 and P11

nervous system

myoclonus ( J:151082 )

♀ • at P7 the incidence of high amplitude movements including sustained spasm-like movements strong enough to cause the pup to flip over, axial contractions that bow or twist the body, and abrupt lateral displacements, is increased

♀ • the frequency of these high amplitude movements decreases between P9 and P11

Genotype
MGI:4353223

ot2

• Allelic Composition: Arx^tm1.1Jno/Y
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

behavior/neurological

abnormal associative learning ( J:151082 )

♂

impaired contextual conditioning behavior ( J:151082 )

♂ • freeze less often than littermate controls when placed in the training environment one day after training

impaired cued conditioning behavior ( J:151082 )

♂ • freeze less often than littermate controls when exposed to the sound cue one day after training

decreased aggression towards mice ( J:151082 )

♂ • in a tube assay mice retreat more frequently compared to littermate controls

decreased anxiety-related response ( J:151082 )

♂ • spend more time in the light and make more light dark transitions in a light/dark exploration assay

♂ • spend 40% more time in the center of an open field compared to littermate controls, with no difference in the amount of movement detected

enhanced coordination ( J:151082 )

♂ • perform significantly better than littermate controls in most trials on a rotarod

decreased thermal nociceptive threshold ( J:151082 )

♂ • 30% shorter latency to hind limb withdrawal

seizures ( J:151082 )

♂ • mice display seizures characterized by 6 Hz spike wave bursts with amplitudes of 150-400 uV accompanied by behavioral arrest

clonic seizures ( J:151082 )

♂ • at 3.5 and 10 weeks of age, spontaneous electrographic seizures characterized by generalized attenuation of the background activity and the appearance of low-voltage fast activity, followed by generalized high frequency and high-amplitude spike and polyspike activity dissipating at different times in different brain regions are seen

♂ • during spontaneous electrographic seizures mice generally make 4 to 10 slow versive movements of the head and/or trunk and clonic movements followed by vigorous grooming

myoclonus ( J:151082 )

♂ • at P7 the incidence of high amplitude movements including sustained spasm-like movements strong enough to cause the pup to flip over, axial contractions that bow or twist the body, and abrupt lateral displacements, is increased

♂ • the frequency of these high amplitude movements decreases between P9 and P11

tonic-clonic seizures ( J:151082 )

♂ • seen in one juvenile male

nervous system

seizures ( J:151082 )

♂ • mice display seizures characterized by 6 Hz spike wave bursts with amplitudes of 150-400 uV accompanied by behavioral arrest

clonic seizures ( J:151082 )

♂ • at 3.5 and 10 weeks of age, spontaneous electrographic seizures characterized by generalized attenuation of the background activity and the appearance of low-voltage fast activity, followed by generalized high frequency and high-amplitude spike and polyspike activity dissipating at different times in different brain regions are seen

♂ • during spontaneous electrographic seizures mice generally make 4 to 10 slow versive movements of the head and/or trunk and clonic movements followed by vigorous grooming

myoclonus ( J:151082 )

♂ • at P7 the incidence of high amplitude movements including sustained spasm-like movements strong enough to cause the pup to flip over, axial contractions that bow or twist the body, and abrupt lateral displacements, is increased

♂ • the frequency of these high amplitude movements decreases between P9 and P11

tonic-clonic seizures ( J:151082 )

♂ • seen in one juvenile male

abnormal brain interneuron morphology ( J:151082 )

♂ • decrease in the number of ARX+ GABAergic interneurons in layers I-VI of the somatosensory and motor cortex

♂ • the number of ARX+ neurons is decreased by about 50% in the hilar region of the dentate gyrus in the hippocampus and in the striatum

♂ • all subtypes of ARX+ GABAergic interneurons are reduced except for the parvalbumin- and calretinin-expressing subtypes

♂ • most striking loss is of the calbindin+ interneurons and this loss is seen in multiple regions

♂ • loss of NPY+ interneurons is confined to the striatum

♂ • severe lack of striatal cholinergic interneurons

♂ • however, no decrease in the number of ARX+ GABAergic interneurons is seen in the parietal cortex

♂ • fewer ARX+ interneurons in the cortex have ARX localized in the nucleus

abnormal striatum morphology ( J:151082 )

♂ • the number of ARX+ neurons is decreased by about 50%

♂ • severe lack of striatal cholinergic interneurons

abnormal hippocampus CA4 region morphology ( J:151082 )

♂ • the number of ARX+ neurons is decreased by about 50%

abnormal cerebral cortex morphology ( J:151082 )

♂ • decrease in the number of ARX+ GABAergic interneurons in layers I-VI of the motor cortex and fewer ARX+ interneurons have ARX localized in the nucleus

abnormal somatosensory cortex morphology ( J:151082 )

♂ • decrease in the number of ARX+ GABAergic interneurons in layers I-VI and fewer ARX+ interneurons have ARX localized in the nucleus

abnormal brain wave pattern ( J:151082 )

♂ • at P16-20,pups display a brief myoclonic jerk that precedes a high-voltage slow transient followed by attenuation of the background EEG amplitude and a transient increase of higher frequency activity

♂ • high-amplitude cortical spikes and sharp waves occur frequently with high voltage slow waves associated with the spike or sharp component

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:151082 )

♂N • unlike null mice, no abnormalities in pancreatic morphology or physiology are detected

muscle

myoclonus ( J:151082 )

♂ • at P7 the incidence of high amplitude movements including sustained spasm-like movements strong enough to cause the pup to flip over, axial contractions that bow or twist the body, and abrupt lateral displacements, is increased

♂ • the frequency of these high amplitude movements decreases between P9 and P11

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
early infantile epileptic encephalopathy		DOID:0050709		J:151082