Phenotypes Associated with This Genotype

Genotype
MGI:8237980

• Allelic Composition: Arid1b^{tm1b(EUCOMM)Hmgu}/Arid1b⁺
• Genetic Background: B6(C)-Arid1b^{tm1b(EUCOMM)Hmgu}
• Cell Lines: HEPD0532_6_C10

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

behavior/neurological

abnormal motor learning ( J:256001 )

• mice show motor learning defects on the rotarod test

abnormal object recognition memory ( J:256001 )

• in the novel object recognition test, mice do not show any preference for exploring either familiar or novel objects indicating impaired recognition memory

• treatment with clonazepam increases the amount of time mice spend investigating the novel object

impaired spatial learning ( J:256001 )

• during the acquisition phase of the Morris water maze, mice show differences in escape latency time after 4 days of training, indicating that capacity for spatial learning is limited, rather than delayed

abnormal long-term spatial reference memory ( J:256001 )

• in the probe trail of the Morris water maze, mice cross the platform location fewer times than controls, however no differences in swimming distances and swimming speeds are seen

• in the T-maze test, mice have a lower success rate of food retrieval compared to controls

decreased coping response ( J:256001 )

• mice exhibit increased immobilization in the forced swim test and tail suspension test

• clonazepam shows no effect on the forced swim test or the tail suspension test

increased anxiety-related response ( J:256001 )

• in the elevated plus maze, mice show increased anxiety

increased thigmotaxis ( J:256001 )

• mice spend less time in the center of the open field test

• clonazepam treatment reverses the reduced time spent in the center

decreased social novelty preference ( J:256001 )

• in the social novelty test, mice spend more time in the chamber containing the first, more familiar, mouse than the second unfamiliar mouse

• while clonazepam treatment does not induce changes in the measured sociability of either control or mutant mice, it rescues the impaired social novelty when a second stranger mouse is introduced

increased grooming behavior ( J:256001 )

• approximately 20% of mice show excessive grooming behavior, resulting in severe self-injury, such as torn ears or hair loss on the face, neck, and shoulder regions

decreased locomotor activity ( J:256001 )

• mice show reduced distance traveled in the open field

• clonazepam treatment reverses the reduced moving distance in the open field test

decreased social investigation ( J:256001 )

• in the three-chamber social test, mice show no preference for either chamber

• in the open field apparatus, mice exhibit reduced time spent on general sniffing, anogenital sniffing, and following behavior

nervous system

increased neuron apoptosis ( J:256001 )

• apoptosis of medial and lateral ganglionic eminence progenitors is increased during development

decreased neuronal precursor proliferation ( J:256001 )

• proliferation of medial ganglionic eminence progenitors is reduced during development

abnormal brain interneuron morphology ( J:256001 )

• GABA+ and parvalbumin+ interneuron densities are decreased in cortices at P91

• other regions in P28 and P91 brains, such as the amygdala, thalamus, and hippocampus, also show reduced numbers of GABA+ and parvalbumin+ interneurons

abnormal cerebral cortex morphology ( J:256001 )

• interneurons are abnormally positioned in cortical layers

• however, lamination patterns of excitatory pyramidal neurons in P28 and P91 cortices show grossly normal CUX1 and TBR1 layering patterns and no changes in the densities of somatostatin+, calbindin+, and calretinin+ cells in the cortices are seen

• GABA+ and parvalbumin+ neuron densities are decreased in cortices at P91

abnormal lateral ganglionic eminence morphology ( J:256001 )

• the numbers of apoptotic cells are increased in the lateral ganglionic eminences

abnormal medial ganglionic eminence morphology ( J:256001 )

• the number of proliferating ventral progenitor cells in the medial ganglionic eminence (MGE) is decreased

• the numbers of apoptotic cells are increased in the medial ganglionic eminence; these apoptotic cells are progenitor cells

• the number of proliferating progenitors in cultured MGE progenitors are decreased and the number of apoptotic cells in cultured MGE progenitors are increased

abnormal synapse morphology ( J:256001 )

• the ratio of SLC17a7+ to SLC32a1+ synapses in cortical layers II/III shows a higher ratio of excitatory to inhibitory synapses, suggesting excitatory-inhibitory imbalance

abnormal postsynaptic density morphology ( J:256001 )

• length of postsynaptic density is shorter in P91 cortices

abnormal inhibitory synapse morphology ( J:256001 )

• mice exhibit abnormal formation of inhibitory synapses

• the number of inhibitory synapses (SLC32a1+ and GAD2+) is reduced in cortices at P91

• however, no change in the number of excitatory synapses (SLC17a7+) in cortices

• markers of inhibitory postsynapses are decreased while levels of excitatory postsynapse makers are unchanged in the cortices

abnormal symmetric synapse morphology ( J:256001 )

• cortices at P91 show an increase in cleft width of symmetric synapses compared with controls, and have a decreased length of postsynaptic density

abnormal inhibitory postsynaptic currents ( J:256001 )

• the frequency of miniature inhibitory postsynaptic currents (mIPSC) is decreased and interevent interval is increased in cortical neurons

• however, mIPSC amplitude is not different

• no changes are seen in the frequency, interevent interval, or amplitude of miniature excitatory postsynaptic currents (mEPSC) in cortical neurons

• clonazepam treatment reverses the decreased mIPSC frequency

cellular

increased neuron apoptosis ( J:256001 )

• apoptosis of medial and lateral ganglionic eminence progenitors is increased during development

decreased neuronal precursor proliferation ( J:256001 )

• proliferation of medial ganglionic eminence progenitors is reduced during development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:256001
intellectual disability		DOID:1059		J:256001