Phenotypes associated with this allele

• Allele Symbol: Syn2^tm1Pggd
• Allele Name: targeted mutation 1, Paul Greengard
• Allele ID: MGI:3045984
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Syn2^tm1Pggd/Syn2^tm1Pggd	B6.1129-Syn2^tm1Pggd	MGI:5517484
hm2	Syn2^tm1Pggd/Syn2^tm1Pggd	Not Specified	MGI:3045985
cx3	Syn1^tm1Pggd/Syn1^tm1Pggd Syn2^tm1Pggd/Syn2^tm1Pggd Syn3^tm1Pggd/Syn3^tm1Pggd	involves: 129 * 129P2/OlaHsd * 129X1/SvJ * C57BL/6	MGI:5698534
cx4	Syn1^tm1Pggd/Syn1^tm1Pggd Syn2^tm1Pggd/Syn2^tm1Pggd	involves: 129P2/OlaHsd	MGI:3045986

Genotype
MGI:5517484

hm1

• Allelic Composition: Syn2^tm1Pggd/Syn2^tm1Pggd
• Genetic Background: B6.1129-Syn2^tm1Pggd

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

behavior/neurological

abnormal emotion/affect behavior ( J:201707 )

♂ • mutants bury fewer marbles than controls when placed in a cage with new bedding and marbles and this behavior is associated with reduced time spent in digging, whereas rearing behavior is unchanged

♂ • after habituation to marbles, mutants still bury less marbles than controls, suggesting this behavior is no due to an altered response to novelty but a decrease in interest toward the environment

♂ • however, mutants exhibit normal anxiety related behaviors

increased aggression towards mice ( J:201707 )

♂ • in the social dominance tube test, adults show more dominant behavior than controls

increased grooming behavior ( J:201707 )

♂ • young and adult mutants exhibit increased repetitive self-grooming behavior

abnormal social investigation ( J:201707 )

♂ • in a modified three-chamber social approach test, mutants exhibit reduced interest for both the social stimulus (unfamiliar stranger mouse) and the novel empty cup

♂ • in the social novelty test, young and adult mutants do not discriminate between familiar and novel mice compared to controls that spend more time exploring the novel mouse than a familiar mouse

♂ • in the resident-intruder test, mutants show reduced social interaction with the intruder mice after 1-2 months of social isolation

decreased social investigation ( J:201707 )

♂ • in the social recognition test, adults spend a similar time in exploring the intruder mouse during all sessions and both young and adult mutants do not increase the exploration of the novel intruder mouse on the fifth session, indicating defective short-term social recognition

taste/olfaction

taste/olfaction phenotype ( J:201707 )

♂N • olfaction is intact

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:201707

Genotype
MGI:3045985

hm2

• Allelic Composition: Syn2^tm1Pggd/Syn2^tm1Pggd
• Genetic Background: Not Specified

nervous system

seizures ( J:202031 )

• epileptic seizures in adults

abnormal brain morphology ( J:91113 )

decreased brain weight ( J:91113 )

• at E16, brain weight was 17% lower than normal

• by E19 the brain weight reduction was only 12%

delayed CNS synapse formation ( J:91113 )

• synapse formation is delayed 2-3 days in culture

abnormal neuron morphology ( J:91113 )

• neurons in culture are arrested in an undifferentiated stage prior to axon formation

abnormal synaptic vesicle number ( J:202031 )

• the number of synaptic vesicles within the mossy fiber terminals in the hilar region of the dentate gyrate is reduced, however the total number of docked synaptic vesicles does not differ

abnormal hippocampus physiology ( J:202031 )

• pre-symptomatic mutants exhibit network impairments of the dentate gyrus, showing reduced mean amplitude of the response in the hilar region and a longer propagation time of evoked field postsynaptic potentials (fPSP), indicating decreased activity in the hilus upon stimulation of the perforant path

• hilar mossy cells of both young pre-symptomatic and older symptomatic (4-6 months) mice exhibit decreased excitability, showing a lower firing rate, an increase in the rheobase, and reduced input resistance

• however, granule cell excitability is normal

abnormal CNS synaptic transmission ( J:202031 )

• reduction in synaptic activity in dentate gyrus mossy cells of young pre-symptomatic mutants

• inhibitory output of hilar mossy cells to granule cells is reduced in both pre-symptomatic and symptomatic mutants; 40Hz tetanic stimulation results in an increase in depression at inhibitory synapses in granule neurons, however it is similar to wild-type at excitatory synapses, and the ratio between the evoked excitatory and inhibitory responses on the same granule cell is increased for the last 10 responses of the train, with a decrease of inhibitory responses

abnormal excitatory postsynaptic potential ( J:202031 )

• pre-symptomatic mutants exhibit a longer propagation time of evoked field postsynaptic potentials in the hilar region of the dentate gyrus

abnormal miniature excitatory postsynaptic currents ( J:202031 )

• hilar mossy cells of the dentate gyrus of both pre-symptomatic and symptomatic mutants show a reduction in miniature excitatory postsynaptic current (mEPSC) frequency and amplitude after blocking GABA receptors and NA+ channels with bicucalline indicating a decrease in excitatory presynaptic input on hilar mossy cells

decreased synaptic depression ( J:202031 )

• the depression induced by a train of stimuli (20 Hz for 5s) is reduced in hippocampal slices of young mutants, suggesting a reduced feedback inhibition of the granule cell layer

behavior/neurological

seizures ( J:202031 )

• epileptic seizures in adults

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
epilepsy		DOID:1826		J:202031

Genotype
MGI:5698534

cx3

• Allelic Composition: Syn1^tm1Pggd/Syn1^tm1Pggd; Syn2^tm1Pggd/Syn2^tm1Pggd; Syn3^tm1Pggd/Syn3^tm1Pggd
• Genetic Background: involves: 129 * 129P2/OlaHsd * 129X1/SvJ * C57BL/6

behavior/neurological

environmentally induced seizures ( J:175256 )

♀ • opening of the home cage of adult mutants induces generalized tonic-clonic seizures that correlate with high amplitude and high frequency generalized synchronized activity followed by post-ictal depression in the theta frequency rage (3-6 Hz)

♀ • seizures commence within seconds of cage opening and include vocalization, freezing, tail stiffing, back arching, bilateral limb movements, and loss of posture, followed by stereotypical grooming behavior

♀ • the symptomatic seizure state is characterized by resistance to the epileptiform-promoting effects of 4-aminopyridine, by hypersensitivity to blockage of GABA(A) receptors and by the emergence of unresponsiveness to NMDA receptor antagonism

tonic-clonic seizures ( J:175256 )

♀ • opening of the home cage of adult mutants induces generalized tonic-clonic seizures

♀ • however, mice exhibit spontaneous seizures only vary rarely

nervous system

environmentally induced seizures ( J:175256 )

♀ • opening of the home cage of adult mutants induces generalized tonic-clonic seizures that correlate with high amplitude and high frequency generalized synchronized activity followed by post-ictal depression in the theta frequency rage (3-6 Hz)

♀ • seizures commence within seconds of cage opening and include vocalization, freezing, tail stiffing, back arching, bilateral limb movements, and loss of posture, followed by stereotypical grooming behavior

♀ • the symptomatic seizure state is characterized by resistance to the epileptiform-promoting effects of 4-aminopyridine, by hypersensitivity to blockage of GABA(A) receptors and by the emergence of unresponsiveness to NMDA receptor antagonism

tonic-clonic seizures ( J:175256 )

♀ • opening of the home cage of adult mutants induces generalized tonic-clonic seizures

♀ • however, mice exhibit spontaneous seizures only vary rarely

abnormal brain wave pattern ( J:175256 )

♀ • EEG indicates an abrupt transition during early adulthood from a seizure-free presymptomatic latent state to a consistent symptomatic state of sensory-induced seizures

♀ • EEG indicates that during the latent period, larger field responses are elicited in slices from mutants than in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
epilepsy		DOID:1826		J:175256

Genotype
MGI:3045986

cx4

• Allelic Composition: Syn1^tm1Pggd/Syn1^tm1Pggd; Syn2^tm1Pggd/Syn2^tm1Pggd
• Genetic Background: involves: 129P2/OlaHsd

nervous system

nervous system phenotype ( J:91113 )

♀N • abnormal neuron phenotype was restored

♀N • brain weight was normal

abnormal CNS synapse formation ( J:91113 )

♀ • synapse formation is delayed 2-3 days in culture