Phenotypes associated with this allele

• Allele Symbol: Cplx1^tm2Bros
• Allele Name: targeted mutation 2, Nils Brose
• Allele ID: MGI:2679624
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cplx1^tm2Bros/Cplx1^tm2Bros	Not Specified	MGI:2679647
cx2	Cplx1^tm2Bros/Cplx1^tm2Bros Cplx2^tm1Bros/Cplx2^tm1Bros	Not Specified	MGI:2679648
cx3	Cplx1^tm2Bros/Cplx1^tm2Bros Cplx2^tm1Bros/Cplx2^tm1Bros Cplx3^tm1Bros/Cplx3^tm1Bros	Not Specified	MGI:3807187

Genotype
MGI:2679647

hm1

• Allelic Composition: Cplx1^tm2Bros/Cplx1^tm2Bros
• Genetic Background: Not Specified

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

mortality/aging

premature death ( J:86365 )

• affected animals die within 2-4 months

behavior/neurological

ataxia ( J:86365 )

abnormal sexual interaction ( J:145652 )

♂ • males cannot mate due to ataxia

sporadic seizures ( J:86365 )

• exhibit sporadic seizures, however no obvious brain structure abnormalities are seen

reproductive system

reproductive system phenotype ( J:145652 )

♂N • mutant sperm show no significant changes in morphology, number, capacitation or spontaneous acrosome reaction rate relative to wild-type sperm

♂N • in addition, capacitated mutant sperm display a normal ability to bind the zona pellucida of oocytes

asthenozoospermia ( J:145652 )

♂ • mutant sperm show only a small difference in normal motility and hyperactivation parameters, as assessed by computer-assisted semen analysis; however, this small motility difference is only evident before 60 min of capacitation

infertility ( J:86365 )

• unable to reproduce

male infertility ( J:145652 )

♂ • males cannot mate and fail to reproduce because of ataxia

♂ • in addition, mutant sperm are subfertile due to defective zona pellucida penetration

impaired fertilization ( J:124872 )

• in vitro, the fertilization rate of cumulus-enclosed oocytes by capacitated mutant sperm is reduced to ~50% of that observed for wild-type sperm

impaired acrosome reaction ( J:124872 , J:145652 )

♂ • in vitro, mutant sperm are unable to acrosome react in response to soluble zona pellucida proteins; only ~25% of capacitated mutant sperm are shown to acrosome react vs ~42% of wild-type sperm, despite a surprising upregulation of complexin 2 expression in mutant testes (J:124872)

♂ • notably, mutant sperm are capable of triggering exocytosis in response to the large calcium influx induced by A23187, with no significant differences in acrosome reaction frequency relative to wild-type sperm (~73% vs ~77%, respectively) (J:124872)

♂ • no differences in the in vitro fertilization rate of zona-free oocytes are observed between wild-type and mutant sperm, indicating that the fertilizing ability of mutant sperm is restored to normal levels upon removal of the zona pellucida (J:145652)

nervous system

sporadic seizures ( J:86365 )

• exhibit sporadic seizures, however no obvious brain structure abnormalities are seen

abnormal neuron physiology ( J:150417 )

• in endbulb synapses the probability of release of vesicles is about 4 fold lower than in controls

• bushy cell spike probability is lower at the beginning stimulation train but approaches wild-type levels later in the train

• endbulbs display increased delayed release and misplaced spikes

• sound thresholds are significantly elevated in anteroventral cochlear nucleus cells

• first spike latencies are prolonged and synaptic jitter is increased in bushy cells

decreased excitatory postsynaptic current amplitude ( J:150417 )

• initial EPSCs of endbulb synapses are about 5 fold smaller compared to controls

decreased miniature excitatory postsynaptic current frequency ( J:150417 )

• significantly lower mEPSC frequency in endbulb synapses

abnormal paired-pulse inhibition ( J:150417 )

• endbulb synapses fail to show depression in response at any pulse interval tested

hearing/vestibular/ear

abnormal hearing electrophysiology ( J:150417 )

• a threshold increase is seen auditory steady-state responses that is comparable to that of the threshold increase in brainstem auditory evoked potentials

abnormal auditory brainstem response waveform shape ( J:150417 )

• young mice show an amplitude reduction and progressive delay of the central auditory ABR peaks

• the peak delay is disproportionately increased by hypothermia

increased or absent threshold for auditory brainstem response ( J:150417 )

• small threshold increase in the midfrequency range is seen at 3-4 weeks of age

• this impairment is increased at 6-10 weeks of age

growth/size/body

decreased body size ( J:145652 )

♂ • male homozygotes are much smaller than wild-type littermates

♂ • reduced body size is probably due to difficulty in consuming food, caused by ataxia

cellular

asthenozoospermia ( J:145652 )

♂ • mutant sperm show only a small difference in normal motility and hyperactivation parameters, as assessed by computer-assisted semen analysis; however, this small motility difference is only evident before 60 min of capacitation

Genotype
MGI:2679648

cx2

• Allelic Composition: Cplx1^tm2Bros/Cplx1^tm2Bros; Cplx2^tm1Bros/Cplx2^tm1Bros
• Genetic Background: Not Specified

mortality/aging

neonatal lethality, complete penetrance ( J:86365 , J:136393 )

• die within a few hours of birth (J:86365)

• mice die within a few hours of birth (J:136393)

nervous system

abnormal pre-Botzinger complex physiology ( J:136393 )

• the amplitude of spontaneous excitatory postsynaptic currents are decreased in pre-Botzinger complex neurons compared to in wild-type mice

abnormal neuron physiology ( J:136393 )

• neuron calcium sensitivity of glutamate and GABA release is reduced compared to in wild-type mice

impaired synaptic plasticity ( J:136393 )

• trains of action potentials produce a marked initial facilitation compared to the depression observed in wild-type mice

abnormal CNS synaptic transmission ( J:86365 )

• defect coupling action potential to presynaptic release

• hippocampal EPSC amplitudes reduced 66% but increases with trains of stimuli

• affect is on fast synchronous release

• much less of neurotransmitter released

• decreased Ca+2 sensitivity

decreased excitatory postsynaptic current amplitude ( J:136393 )

• evoked and spontaneous excitatory postsynaptic current amplitudes in hippocampal neurons are reduced compared to in wild-type mice

• the amplitude of spontaneous excitatory postsynaptic currents are decreased in pre-Botzinger complex neurons compared to in wild-type mice

abnormal inhibitory postsynaptic currents ( J:136393 )

• mice exhibit a reduced evoked inhibitory postsynaptic currents and slightly reduced miniature inhibitory postsynaptic currents compared to wild-type mice

• spontaneous miniature inhibitory postsynaptic current frequencies are decreased in hippocampal and pre-Botzinger complex neurons compared to in wild-type mice

decreased miniature excitatory postsynaptic current amplitude ( J:136393 )

• evoked miniature excitatory postsynaptic currents (mEPSCs) are slightly reduced while spontaneous mEPSCs are reduced 30% compared to in wild-type mice

decreased miniature excitatory postsynaptic current frequency ( J:136393 )

• spontaneous mEPSC frequencies are decreased in hippocampal neurons and pre-Botzinger complex neurons compared to in wild-type mice

abnormal neurotransmitter secretion ( J:136393 )

• the probability of vesicular release of the readily releasable pool is reduced 50% compared to in wild-type mice

• neuron calcium sensitivity of glutamate and GABA release is reduced compared to in wild-type mice

• however, the size of the readily releasable pool is normal

Genotype
MGI:3807187

cx3

• Allelic Composition: Cplx1^tm2Bros/Cplx1^tm2Bros; Cplx2^tm1Bros/Cplx2^tm1Bros; Cplx3^tm1Bros/Cplx3^tm1Bros
• Genetic Background: Not Specified

mortality/aging

neonatal lethality, complete penetrance ( J:136393 )

• mice die within a few hours of birth

nervous system

abnormal pre-Botzinger complex physiology ( J:136393 )

• the amplitude and frequency of spontaneous excitatory postsynaptic currents are decreased in pre-Botzinger complex neurons compared to in wild-type mice

• spontaneous mEPSC frequencies are decreased in hippocampal neurons and pre-Botzinger complex neurons compared to in wild-type

abnormal neuron physiology ( J:136393 )

• neuron calcium sensitivity of glutamate and GABA release is reduced compared to in wild-type mice

impaired synaptic plasticity ( J:136393 )

• trains of action potentials produce a marked initial facilitation compared to a the depression observed in wild-type mice

decreased excitatory postsynaptic current amplitude ( J:136393 )

• evoked and spontaneous excitatory postsynaptic current amplitudes in hippocampal neurons are reduced compared to in wild-type mice

• in pre-Botzinger complex neurons compared to in wild-type mice

decreased excitatory postsynaptic current frequency ( J:136393 )

• in pre-Botzinger complex neurons compared to in wild-type mice

abnormal inhibitory postsynaptic currents ( J:136393 )

• mice exhibit a reduced evoked inhibitory postsynaptic currents and slightly reduced miniature inhibitory postsynaptic currents compared to wild-type mice

• spontaneous miniature inhibitory postsynaptic current frequencies are decreased in hippocampal and pre-Botzinger complex neurons compared to in wild-type mice

abnormal miniature excitatory postsynaptic currents ( J:136393 )

• evoked miniature excitatory postsynaptic currents (mEPSCs) are slightly reduced while spontaneous mEPSCs are reduced 30% compared to in wild-type mice

• spontaneous mEPSC frequencies are decreased in hippocampal neurons and pre-Botzinger complex neurons compared to in wild-type mice

• the amplitude of spontaneous mEPSC in hippocampal neurons is decreased compared to in wild-type mice

abnormal neurotransmitter secretion ( J:136393 )

• the probability of vesicular release of the readily releasable pool is reduced 50% compared to in wild-type mice

• neuron calcium sensitivity of glutamate and GABA release is reduced compared to in wild-type mice

• however, the size of the readily releasable pool is normal