Phenotypes Associated with This Genotype

Genotype
MGI:6115507

• Allelic Composition: Kctd13^{tm1.1(KOMP)Vlcg}/Kctd13^{tm1.1(KOMP)Vlcg}
• Genetic Background: involves: C57BL/6J * C57BL/6NTac

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

nervous system

nervous system phenotype ( J:250125 )

N • homozygotes show no changes in indirect measures of presynaptic release probability, as paired-pulse facilitation and the rate of decay of NMDAR-mediated excitatory postsynaptic currents in the presence of MK-801 are normal

N • no changes in multiple measures of brain size, embryonic and adult brain cell proliferation, neurogenesis, or cortical layering/migration are observed

decreased dendritic spine density ( J:250125 )

• CA1 pyramidal neurons show a significant reduction in dendritic spine density

abnormal hippocampal pyramidal neuron dendrite morphology ( J:250125 )

• CA1 pyramidal neurons show a significant reduction in dendritic length, branching complexity, and dendritic spine density

abnormal excitatory synapse morphology ( J:250125 )

• homozygotes show a reduction in functional excitatory synapse number

abnormal CNS synaptic transmission ( J:250125 )

• homozygotes show significantly reduced synaptic transmission in the CA1 region of the hippocampus relative to wild-type controls

• reduced synaptic transmission correlates with increased levels of RhoA (ras homolog family member A), a KCTD13/CUL3 ubiquitin ligase substrate, after P7 and is reversed by RhoA inhibition

abnormal excitatory postsynaptic potential ( J:250125 )

• homozygotes show a ~50% reduction of field excitatory postsynaptic potential (fEPSP) slope relative to wild-type controls

• hippocampal slice incubation with a RhoA/B/C inhibitor (rhosin or C3) reverses the fEPSP slope deficit to vehicle-treated wild-type levels

abnormal miniature excitatory postsynaptic currents ( J:250125 )

• miniature excitatory postsynaptic current (mEPSC) frequency is significantly decreased in CA1 pyramidal neurons relative to wild-type controls, with no change in the amplitude of mEPSCs

• mEPSC frequency is significantly decreased in somatosensory cortical layer 2/3 neurons, with no change in the amplitude of mEPSCs

• hippocampal slice incubation with the RhoA/B/C inhibitor rhosin rescues the reduction in mEPSC frequency to vehicle-treated wild-type levels

decreased miniature inhibitory postsynaptic current frequency ( J:250125 )

• miniature inhibitory postsynaptic current (mIPSC) frequency is significantly decreased in somatosensory cortical layer 2/3 neurons relative to wild-type controls; however, CA1 pyramidal neuron mIPSC amplitude is normal

behavior/neurological

increased locomotor activity ( J:250125 )

• homozygotes show increased locomotor activity relative to wild-type controls, as determined by the total number of photobeam breaks over a 2 hr period

growth/size/body

growth/size/body region phenotype ( J:250125 )

N • homozygotes exhibit normal body weight at 12 weeks of age