All Phenotypes Rbfox3<tm1a(EUCOMM)Hmgu> MGI Mouse

nervous system phenotype ( J:234043 , J:240501 )

N	• surprisingly, dentate granule neurons and CA1 pyramidal neurons of adult (P49) mice exhibit normal intrinsic excitability (J:234043) • adult mice exhibit normal prepulse inhibition (PPI), as determined by an acoustic startle response assay (J:240501)

increased susceptibility to pharmacologically induced seizures ( J:234043 )

• treatment of 14-week-old mice with kainic acid results in significantly higher seizure scores and fatality than in wild-type controls

• however, no spontaneous seizures are detected during one week of continuous observation

abnormal neuron differentiation ( J:240501 )

• mice show deficits in adult neurogenesis, as shown by a significant reduction in the number of DCX- and Ki-67-positive cells in the hippocampal dentate gyrus

decreased neuronal precursor proliferation ( J:240501 )

• mice show a significant reduction in the number of Ki-67-positive proliferating cells in the hippocampal dentate gyrus

decreased brain weight ( J:234043 )

• brain weight is significantly reduced, regardless of gender

• however, no major defects in brain morphology are observed

abnormal brain white matter morphology ( J:234043 )

• total volume of white matter is reduced, as demonstrated by neurofilament and MRI data

abnormal hippocampus neuron morphology ( J:234043 )

• mice show impaired neurofilament expression in the hippocampus, indicating loss of neuronal integrity

• total neurofilament heavy chain (NF200-H), and active (pNF-H) and inactive (NF-H) forms of neurofilament heavy chains are reduced; neurofilament light chain (NF-L) and medium chain (NF-M) are also reduced

abnormal hippocampus granule cell morphology ( J:234043 )

• adult mice show increased spine density and dendritic complexity in hippocampal granule cells

increased dendritic spine density ( J:234043 )

• adult mice show increased dendritic spine density of dentate granule cells

abnormal dentate gyrus neuron dendrite morphology ( J:234043 )

• adult mice show increased spine density in the distal and proximal regions of dendrites of dentate gyrus granule cells

• Sholl analysis and dendritic morphology analysis revealed increased dendritic complexity

decreased neuronal precursor cell number ( J:240501 )

• mice show a significant reduction in the number of DCX-positive immature neurons in the hippocampal dentate gyrus

abnormal excitatory synapse morphology ( J:240501 )

• mice exhibit a significant increase in the density of excitatory synapses in the dendrites of hippocampal dentate granule cells relative to wild-type controls

• however, no change in the size of the pre- or postsynaptic sites is observed

abnormal hippocampus physiology ( J:234043 )

• mice show an increased expression of the immediate early plasticity genes Egr4 and Arc in the hippocampus

impaired synaptic plasticity ( J:234043 , J:240501 )

(J:234043)

• mice exhibit decreased synaptic plasticity in the hippocampal dentate gyrus (J:240501)

abnormal CNS synaptic transmission ( J:234043 )

• hippocampal granule cells of adult mice exhibit increased frequency but normal amplitude of excitatory and inhibitory neurotransmission

abnormal excitatory postsynaptic potential ( J:234043 , J:240501 )

• mice exhibit normal presynaptic fiber volley amplitudes but increased postsynaptic field excitatory postsynaptic potential (fEPSP) slopes relative to wild-type controls (J:234043)

• following DHPG treatment, fEPSP slope (% of baseline) is increased relative to that in DHPG-treated wild-type controls (J:240501)

abnormal miniature inhibitory postsynaptic currents ( J:234043 )

• both young (P19) and adult (P49) mice show increased mIPSC frequency in granule cells of the dentate gyrus

• however, mIPSC amplitude is normal

increased miniature inhibitory postsynaptic current frequency ( J:234043 )

• both young (P19) and adult (P49) mice show increased mEPSC frequency in granule cells of the dentate gyrus

• adult mice also show increased mEPSC frequency in CA1 pyramidal neurons

• however, mEPSC amplitude is normal

reduced long-term depression ( J:234043 , J:240501 )

• long-term depression (LTD) induced by low frequency stimulation is significantly reduced in the dentate gyrus relative to wild-type controls; LTD deficits are also observed in the hippocampal CA1 region (J:234043)

• in contrast, long-term potentiation (LTP) induced by theta burst stimulation is normal in the dentate gyrus (J:234043)

• LTD induced by the agonist 3,5-dihydroxyphenlyglycine (DHPG) is significantly reduced in the dentate gyrus relative to wild-type controls (J:240501)

• DHPG-induced LTD deficits cannot be rescued by treatment with the protein kinase C agonist, bryostatin-1 (J:240501)

increased neurotransmitter release ( J:234043 )

• adult mice show an increase in neurotransmitter release probability

decreased paired-pulse facilitation ( J:234043 )

• the paired-pulse ratio is reduced at different interpulse intervals, suggesting that synaptic transmitter release probability is increased

behavior/neurological phenotype ( J:240501 )

N	• adult mice exhibit normal motor coordination and grip force, as determined by rotarod, gait analysis and grip force tests

increased susceptibility to pharmacologically induced seizures ( J:234043 )

• treatment of 14-week-old mice with kainic acid results in significantly higher seizure scores and fatality than in wild-type controls

• however, no spontaneous seizures are detected during one week of continuous observation

abnormal object recognition memory ( J:240501 )

• adult mice exhibit learning deficits in a novel object recognition test relative wild-type controls

impaired spatial learning ( J:234043 )

• in the Morris water maze test, mice show moderate deficits in the acquisition of spatial learning during early assessments (day 2-6) with no significant difference after day 6, suggesting a delay in spatial learning

• a prolonged deficit is observed in spatial reversal learning

• visual learning is impaired in the visible platform test; however, further tests of visual acuity are required

decreased anxiety-related response ( J:234043 )

• when food-deprived and placed in a new environment, mice are faster to initiate feeding than wild-type controls; however, latency to feed is normal when mice are presented with food in a familiar environment

• mice exhibit decreased marble-burying behavior relative to wild-type controls

• mice spend more time in open arms in the elevated plus-maze test; however, there is no variability in the total time in the arms or number of entries into open arms relative to wild-type controls, suggesting that motor function is normal

• in an open field test, mice spend more active time in open and bright areas than wild-type controls; however, total walking distance, walking speed, and rearing numbers are normal

increased locomotor activity ( J:234043 )

• in the elevated plus-maze test, mice show a greater total number of entries into arms than wild-type controls, suggesting hyperactivity

abnormal thermal nociception ( J:240501 )

• adult mice exhibit significant cold hyperalgesia in the cold plate test; average latency in response to a 0.0 +/- 1.0 degree Celsius stimulus is significantly lower than in wild-type controls within a 50 second cut-off time

• however, average latency in response to a 55.0 +/- 1 degree Celsius stimulus is normal in the hot plate test

increased susceptibility to xenobiotic induced morbidity/mortality ( J:234043 )

• treatment of 14-week-old mice with kainic acid results in a significantly increased death rate (+17.65%) relative to wild-type controls