Phenotypes associated with this allele

• Allele Symbol: Adgrb1^tm1Egvm
• Allele Name: targeted mutation 1, Erwin G Van Meir
• Allele ID: MGI:5755487
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adgrb1^tm1Egvm/Adgrb1^tm1Egvm	involves: 129S6/SvEvTac * C57BL/6	MGI:6459227

Genotype
MGI:6459227

hm1

• Allelic Composition: Adgrb1^tm1Egvm/Adgrb1^tm1Egvm
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

behavior/neurological

behavior/neurological phenotype ( J:222100 )

N • mice show normal anxiety-like behavior, as assessed by the elevated plus-maze test, the marble-burying test and the light/dark test

abnormal learning/memory/conditioning ( J:222100 )

• mice exhibit severe deficits in hippocampus-dependent spatial learning and memory tasks

impaired spatial learning ( J:222100 )

• in the hidden-platform version of the Morris water-maze test, mice fail to show a progressive decrease in their escape latency over the period of acquisition, unlike wild-type controls

• during a probe trial (wherein the platform is removed), mice fail to show a preference for the target quadrant, unlike wild-type controls

• however, no differences in escape latencies or distance traveled are observed during the visible-platform Morris water maze test

nervous system

nervous system phenotype ( J:222100 )

N • surprisingly, mice exhibit normal brain structure with no apparent defects in brain vasculature; no brain tumors are detected up to 1.5 year of age

N • adult hippocampal CA1 pyramidal neurons exhibit normal dendritic arborization and spine morphology

abnormal hippocampus pyramidal cell morphology ( J:222100 )

• hippocampal CA1 pyramidal neurons exhibit thinning of the postsynaptic density (PSD)

abnormal postsynaptic density morphology ( J:222100 )

• adult hippocampal CA1 pyramidal neurons exhibit a 40% reduction in postsynaptic density (PSD) thickness, with a smaller reduction noted at 3 weeks of age

• a ~40% reduction in PSD thickness is also observed in adult cortex somatosensory neurons

impaired synaptic plasticity ( J:222100 )

• mice show striking alterations in frequency-dependent synaptic plasticity in CA1 pyramidal neurons

• alterations in synaptic plasticity are primarily postsynaptic, as the paired-pulse ratio of evoked excitatory postsynaptic currents (eEPSCs, a measure of short-term presynaptic plasticity) is normal

• restoration of PSD-95 in adult hippocampal neurons by viral gene therapy reverses the synaptic plasticity deficits, suggesting that impaired synaptic plasticity is largely due to destabilization of PSD-95

enhanced long-term potentiation ( J:222100 )

• enhanced NMDAR-dependent long-term potentiation (LTP) induction in CA1 pyramidal neurons following high-frequency stimulation using 5 x 100 Hz trains of stimulation at 20-sec intervals

• a low-frequency stimulation protocol (900 pulses delivered at 1 Hz), that normally induces stable long- term depression (LTD) in wild-type slices, induces a sharp enhancement of LTP

reduced long-term depression ( J:222100 )

• a low-frequency stimulation protocol (900 pulses delivered at 1 Hz) fails to induce LTD in hippocampal slices, suggesting loss of LTD in hippocampal CA1 synapses

homeostasis/metabolism

abnormal protein level ( J:222100 )

• brains show a ~50% reduction in protein, but not mRNA, levels of PSD-95 (a canonical postsynaptic density component that regulates synapse maturation and synaptic plasticity), with similar decreases noted in the neocortex, hippocampus, and cerebellum

• analysis of PSD-95 levels in purified PSD fractions revealed a marked reduction in the post-synaptic compartment

• in culture, primary cortical neurons treated with cycloheximide (a protein synthesis blocker) show a 2-fold increase in the degradation rate of PSD-95 relative to wild-type neurons