Phenotypes associated with this allele

• Allele Symbol: Nrxn2^tm1Sud
• Allele Name: targeted mutation 1, Thomas C Sudhof
• Allele ID: MGI:3042719
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nrxn2^tm1Sud/Nrxn2^tm1Sud	involves: 129 * C57BL/6 * C57BL/6J * C57BL/6NClr	MGI:5632308
cx2	Nrxn1^tm1Sud/Nrxn1^tm1Sud Nrxn2^tm1Sud/Nrxn2^tm1Sud Nrxn3^tm1Sud/Nrxn3^tm1Sud	involves: 129 * C57BL/6	MGI:3043352
cx3	Nrxn1^tm1Sud/Nrxn1^tm1Sud Nrxn2^tm1Sud/Nrxn2^tm1Sud	involves: 129 * C57BL/6	MGI:4437134
cx4	Nrxn2^tm1Sud/Nrxn2^tm1Sud Nrxn3^tm1Sud/Nrxn3^tm1Sud	involves: 129 * C57BL/6	MGI:4437136

Genotype
MGI:5632308

hm1

• Allelic Composition: Nrxn2^tm1Sud/Nrxn2^tm1Sud
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * C57BL/6NClr

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

behavior/neurological

increased anxiety-related response ( J:220076 )

• in the open field, mutants spend more time in the peripheral zone near the walls and less time in the intermediate zone, than wild-type mice, however the total distance traveled is not different

• in the elevated plus maze, mutants spend less time in the open arms and more time in the closed arms, make fewer exploratory head dips from the center and open arms, and spend less time on the central square

• in the emergence test, mutants take 3.7 times longer than wild-type mice to emerge from a small enclosure, spend more time in the enclosure and make fewer entries into the open arena

• mutants exhibit normal behavior in the Porsolt forced-swim test and tail suspension test, indicating absence of depression-related behaviors

• mice exhibit normal long term memory in passive avoidance learning

abnormal response to novel object ( J:220076 )

• in the novel object test, mutants spend les time exploring a novel object than wild-type mice, however locomotor activity is normal during both habituation and test phases

increased vertical activity ( J:220076 )

• mutants spend more time rearing than wild-type mice, however no differences in the time spent self-grooming is seen

abnormal social investigation ( J:220076 )

• in the three-chambered assay for sociability, mutants fail to show a preference for the unfamiliar conspecific, however mutants spend an equivalent amount of time in proximity to the empty cage as wild-type mice

• in a social novelty preference test with a choice between the original unfamiliar mouse and a new unfamiliar mouse, mutants do not exhibit a preference for the new unfamiliar mouse as seen in wild-type mice

• in a test of preference for exploring soiled versus clean bedding in the three-chambered assay, mutants show no bias towards either cage unlike wild-type mice which spend more time in the soiled bedding cage, however mutants exhibit a similar latency to find buried food as wild-type mice, indicating normal olfaction

nervous system

nervous system phenotype ( J:220076 )

N • mice show normal startle responses to varying intensities of sound and normal magnitudes of prepulse inhibition

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:220076

Genotype
MGI:3043352

cx2

• 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

cx3

• 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

Genotype
MGI:4437136

cx4

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

mortality/aging

premature death ( J:89452 )

• about 40% survive to P30

postnatal lethality, incomplete penetrance ( J:89452 )

• about 60% survive to P10

nervous system

abnormal excitatory postsynaptic currents ( J:89452 )

• impaired evoked synaptic transmission in brainstem

respiratory system

abnormal breathing pattern ( J:89452 )

• respiration is abnormal with an irregular rhythm