Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nrxn1tm1Sud mutation
(1 available);
any
Nrxn1 mutation
(95 available)
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nervous system
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• although similar amounts of 125I-alpha-latrotoxin bind to brain membranes from homozygous mutant and wild-type mice in the absence of Ca2+, in the presence of Ca2+, 125I-alpha-latrotoxin binding to mutant brain membranes is reduced to about 75% of that to wild-type membranes; binding in the presence of Ca2+ is approximately 2-fold that in its absence
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• in the absence of Ca2+, alpha-latrotoxin-stimulated glutamate release from synaptosomes isolated from homozygous mutant brains is reduced to approximately 80% of that from wild-type synaptosomes
• although in the presence of Ca2+ the kinetics of K+-depolarization-stimulated glutamate release from synaptosomes isolated from homozygous mutant and wild-type brains are similar, the amount of glutamate released from mutant synaptosomes in response to alpha-latrotoxin stimulation is reduced to approximately 25% that from wild-type synaptosomes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nrxn1tm1Sud mutation
(1 available);
any
Nrxn1 mutation
(95 available)
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behavior/neurological
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• mice exhibit no abnormal social behaviors, anxiety-like behaviors, locomotor activity and spatial learning
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• mice exhibit enhanced motor learning on a rotarod compared with wild-type mice
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• increased repetitive grooming
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• mice fail to widen nests unlike wild-type mice
• however, nest height is normal
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nervous system
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• mice exhibit a decrease in the input-output relationship of excitatory synaptic transmission compared with wild-type mice
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• mice exhibit decreased miniature excitatory postsynaptic current (mEPSC) frequency without a change in miniature inhibitory postsynaptic currents compared with wild-type mice
• however, mEPSC amplitude is normal
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nervous system
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• in the presence or in the absence of Ca2+, the amount of 125I-alpha-latrotoxin binding to membranes isolated from brains of doubly homozygous mutant mice is reduced to about 25% of that binding to brain membranes from wild-type mice; approximately twice as much binds in the presence of Ca2+ as in its absence
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• although in the presence of Ca2+ the kinetics are similar for alpha-latrotoxin-stimulated release of glutamate from doubly mutant and wild-type brain-derived synaptosomes, in the absence of Ca2+ the delay to initiation of glutamate release from doubly mutant synaptosomes is prolonged in comparison to that from wild-type and both singly mutant synaptosomes (5 min vs. 2 min)
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• in the absence of Ca2+, alpha-latrotoxin-stimulated glutamate release from synaptosomes isolated from doubly homozygous mutant brains is reduced to approximately 50% of that from wild-type synaptosomes
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mortality/aging
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• all mice die within a day of birth putatively due to dysfunction of essential neural networks involved in breathing
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respiratory system
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• mutants have difficulty breathing with a highly irregular respiratory rhythm and reduced ventilation activity due to a dysfunctional output of rhythm generating network in the brainstem
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nervous system
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• density of symmetric (presumptive inhibitory) synapses are reduced in the brainstem but density of asymmetric (presumptive excitatory) are not
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• post-synaptic defects involving impaired NMDA receptor function
(J:88641)
• decrease in spontaneous miniature postsynaptic current frequency, decrease in evoked response, increase in failure rates, and lack of noticeable changes in postsynaptic receptor activity shows a primary pre-synaptic defect involving impaired neurotransmitter release
(J:89452)
• impaired evoked synaptic transmission in neocortex
(J:89452)
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• large decrease in the frequency of GABA(A)-receptor mediated spontaneous miniature postsynaptic currents in the neocortex and the brainstem
• density of GABA-releasing terminals is reduced by about 2-fold, whereas the density of glutamatergic terminals is unchanged
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• impaired evoked synaptic transmission in brainstem; even at high stimulation strengths, the amplitudes of excitatory postsynaptic currents are smaller than in controls
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• large decrease in the frequency of AMPA-receptor mediated spontaneous miniature postsynaptic currents in the neocortex and the brainstem
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• the NMDA-receptor-dependent component of spontaneous synaptic miniature responses is reduced about 50%, while the AMPA-receptor-dependent component is unaffected
• selective decrease in NMDA-receptor-mediated currents affecting evoked synaptic responses
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• aggravation of short-term synaptic depression within individual stimulus trains and increased synaptic depression during multiple stimulus trains
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• spontaneous and evoked neurotransmitter release is impaired as measured in excitatory and inhibitory synapses in the brainstem and neocortex, partly due to a decrease in presynaptic calcium currents, especially N-type calcium currents
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• within a stimulus train, paired-pulse depression is normal in response to the second stimulus but responses to the 3rd and 4th stimulus are lower in synapses
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mortality/aging
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• about 20% survive to P10
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nervous system
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• density of symmetric (presumptive inhibitory) synapses are reduced in the neocortex but density of asymmetric (presumptive excitatory) synapses are not
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• calcium channels are partly inactivated after synaptic contacts are established resulting in depressed calcium currents
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• impaired evoked synaptic transmission in brainstem
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respiratory system
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• impaired respiration with a highly irregular respiratory rhythm
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