Phenotypes Associated with This Genotype

Genotype
MGI:6278310

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-CHMP2B*)3Fbga/0
• Genetic Background: involves: C57BL/6

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

behavior/neurological

increased thigmotaxis ( J:227797 )

• mice show an age-dependent decrease in thigmotaxis in the elevated-plus-maze test at 4 and 8 months of age

• however, mice exhibit normal behavior in an object recognition task, normal locomotion, and normal olfactory discrimination

increased grooming behavior ( J:227797 )

• 7 of 36 aged mice (14-20 months) exhibit cutaneous lesions that indicate excessive grooming

abnormal social investigation ( J:227797 )

• in the resident-intruder test of social interaction, mice show decreased interaction times at the end of the test, but not at the beginning of the test

• in the three-chamber social paradigm, mice show a more pronounced, age-dependent decrease in sociability, particularly in trial 5, when both social partners are present

• treatment of 8 month old mice with a general AMPAR antagonist, NBQX, increases sociability

• however, treatment with the NMDA receptor antagonist AP5 has no effect on sociability

• mice injected with an adenovirus expressing miR-124 into the medial prefrontal cortex show an increase in sociability 1 month after injection

• mice injected into the medial prefrontal cortex with a lentiviral vector encoding shRNA directed against the AMPAR subunit Gria2 show partial rescue of social deficits

nervous system

abnormal cerebral cortex morphology ( J:227797 )

• 8 month old mice exhibit ubiquitin deposits and an increase of p62 in insoluble fraction in the cortex

• levels of microRNA miR-124 are decreased in the superficial layers of the cerebral cortex

abnormal cerebral cortex pyramidal cell morphology ( J:227797 )

• spine number and density of pyramidal neurons in the superficial layers (II and III) of the medial prefrontal cortex are increased in 8 month old mice; this increase is due to thin spines that are considered to be immature

• however, no spine changes are seen in hippocampal CA3 pyramidal neurons

astrocytosis ( J:227797 )

• 8 month old mice exhibit astrogliosis

increased dendritic spine density ( J:227797 )

• spine density of pyramidal neurons in the superficial layers of the medial prefrontal cortex are increased in 8 month old mice

abnormal CNS synaptic transmission ( J:227797 )

• synapses exhibit a lower rectification index for AMPAR-mediated excitatory postsynaptic currents (EPSCs) and evoked EPSCs of neurons are less sensitive to inhibition by Naspm, a specific inhibitor of calcium-permeable AMPARs, indicating altered AMPAR subunit composition that leads to an imbalance between calcium-permeable and calcium-impermeable AMPARs

• however, neither the amplitude or frequency of AMPAR-mediated miniature excitatory postsynaptic currents are altered

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:227797