Mouse Genome Informatics
hm1
    Nrxn1tm1Sud/Nrxn1tm1Sud
involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• 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


Mouse Genome Informatics
hm2
    Nrxn1tm1Sud/Nrxn1tm1Sud
involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice exhibit no abnormal social behaviors, anxiety-like behaviors, locomotor activity and spatial learning (J:153748)
• increased repetitive grooming
• mice exhibit enhanced motor learning on a rotarod compared with wild-type mice
• mice fail to widen nests unlike wild-type mice
• however, nest height is normal

nervous system
• mice exhibit a decrease in the input-output relationship of excitatory synaptic transmission compared with wild-type mice
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:153748
Schizophrenia; SCZD 181500 J:153748


Mouse Genome Informatics
cx3
    Lphn1tm1Sud/Lphn1tm1Sud
Nrxn1tm1Sud/Nrxn1tm1Sud

involves: 129 * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• 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)
• 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


Mouse Genome Informatics
cx4
    Nrxn1tm1Sud/Nrxn1tm1Sud
Nrxn2tm1Sud/Nrxn2tm1Sud
Nrxn3tm1Sud/Nrxn3tm1Sud

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die within a day of birth putatively due to dysfunction of essential neural networks involved in breathing

respiratory system
• 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

nervous system
• density of symmetric (presumptive inhibitory) synapses are reduced in the brainstem but density of asymmetric (presumptive excitatory) are not
• 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)
• 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
• impaired evoked synaptic transmission in brainstem; even at high stimulation strengths, the amplitudes of excitatory postsynaptic currents are smaller than in controls
• large decrease in the frequency of AMPA-receptor mediated spontaneous miniature postsynaptic currents in the neocortex and the brainstem
• 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
• aggravation of short-term synaptic depression within individual stimulus trains and increased synaptic depression during multiple stimulus trains
• 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
• 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


Mouse Genome Informatics
cx5
    Nrxn1tm1Sud/Nrxn1tm1Sud
Nrxn2tm1Sud/Nrxn2tm1Sud

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 20% survive to P10

nervous system
• density of symmetric (presumptive inhibitory) synapses are reduced in the neocortex but density of asymmetric (presumptive excitatory) synapses are not
• calcium channels are partly inactivated after synaptic contacts are established resulting in depressed calcium currents
• impaired evoked synaptic transmission in brainstem

respiratory system
• impaired respiration with a highly irregular respiratory rhythm