Phenotypes associated with this allele

• Allele Symbol: Nrxn1^tm1Sud
• Allele Name: targeted mutation 1, Thomas C Sudhof
• Allele ID: MGI:3042794
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nrxn1^tm1Sud/Nrxn1^tm1Sud	involves: 129	MGI:3691277
hm2	Nrxn1^tm1Sud/Nrxn1^tm1Sud	involves: 129 * C57BL/6	MGI:5428133
cx3	Adgrl1^tm1Sud/Adgrl1^tm1Sud Nrxn1^tm1Sud/Nrxn1^tm1Sud	involves: 129 * 129S6/SvEvTac * C57BL/6	MGI:3691278
cx4	Nrxn1^tm1Sud/Nrxn1^tm1Sud Nrxn2^tm1Sud/Nrxn2^tm1Sud Nrxn3^tm1Sud/Nrxn3^tm1Sud	involves: 129 * C57BL/6	MGI:3043352
cx5	Nrxn1^tm1Sud/Nrxn1^tm1Sud Nrxn2^tm1Sud/Nrxn2^tm1Sud	involves: 129 * C57BL/6	MGI:4437134

Genotype
MGI:3691277

hm1

• Allelic Composition: Nrxn1^tm1Sud/Nrxn1^tm1Sud
• Genetic Background: involves: 129

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

nervous system

abnormal nervous system physiology ( J:115214 )

• 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

decreased synaptic glutamate release ( J:115214 )

• 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

Genotype
MGI:5428133

hm2

• Allelic Composition: Nrxn1^tm1Sud/Nrxn1^tm1Sud
• Genetic Background: involves: 129 * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:153748 )

N • mice exhibit no abnormal social behaviors, anxiety-like behaviors, locomotor activity and spatial learning

abnormal motor learning ( J:153748 )

• mice exhibit enhanced motor learning on a rotarod compared with wild-type mice

increased grooming behavior ( J:153748 )

• increased repetitive grooming

abnormal nest building behavior ( J:153748 )

• mice fail to widen nests unlike wild-type mice

• however, nest height is normal

nervous system

abnormal excitatory postsynaptic currents ( J:153748 )

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

abnormal miniature excitatory postsynaptic currents ( J:153748 )

• 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

decreased prepulse inhibition ( J:153748 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:153748
schizophrenia		DOID:5419	OMIM:181500	J:153748

Genotype
MGI:3691278

cx3

• Allelic Composition: Adgrl1^tm1Sud/Adgrl1^tm1Sud; Nrxn1^tm1Sud/Nrxn1^tm1Sud
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6

nervous system

abnormal nervous system physiology ( J:115214 )

• 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

abnormal synaptic glutamate release ( J:115214 )

• 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)

decreased synaptic glutamate release ( J:115214 )

• 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

Genotype
MGI:3043352

cx4

• Allelic Composition: Nrxn1^tm1Sud/Nrxn1^tm1Sud; Nrxn2^tm1Sud/Nrxn2^tm1Sud; Nrxn3^tm1Sud/Nrxn3^tm1Sud
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:89452 )

• all mice die within a day of birth putatively due to dysfunction of essential neural networks involved in breathing

respiratory system

respiratory distress ( J:89452 )

• 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

decreased CNS synapse formation ( J:89452 )

• density of symmetric (presumptive inhibitory) synapses are reduced in the brainstem but density of asymmetric (presumptive excitatory) are not

abnormal CNS synaptic transmission ( J:88641 , J:89452 )

• 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)

abnormal GABA-mediated receptor currents ( 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

decreased excitatory postsynaptic current amplitude ( J:89452 )

• impaired evoked synaptic transmission in brainstem; even at high stimulation strengths, the amplitudes of excitatory postsynaptic currents are smaller than in controls

reduced AMPA-mediated synaptic currents ( J:89452 )

• large decrease in the frequency of AMPA-receptor mediated spontaneous miniature postsynaptic currents in the neocortex and the brainstem

reduced NMDA-mediated synaptic currents ( J:88641 )

• 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

abnormal synaptic depression ( J:89452 )

• aggravation of short-term synaptic depression within individual stimulus trains and increased synaptic depression during multiple stimulus trains

decreased neurotransmitter release ( J:89452 )

• 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

abnormal paired-pulse inhibition ( J:89452 )

• 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

Genotype
MGI:4437134

cx5

• Allelic Composition: Nrxn1^tm1Sud/Nrxn1^tm1Sud; Nrxn2^tm1Sud/Nrxn2^tm1Sud
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:89452 )

• about 20% survive to P10

nervous system

decreased CNS synapse formation ( J:89452 )

• density of symmetric (presumptive inhibitory) synapses are reduced in the neocortex but density of asymmetric (presumptive excitatory) synapses are not

abnormal CNS synaptic transmission ( J:89452 )

• calcium channels are partly inactivated after synaptic contacts are established resulting in depressed calcium currents

abnormal excitatory postsynaptic currents ( J:89452 )

• impaired evoked synaptic transmission in brainstem

respiratory system

respiratory distress ( J:89452 )

• impaired respiration with a highly irregular respiratory rhythm