Overview

Also Known As:synapsin II KO

Homozygous synapsin II knockout mice exhibit seizures and retarded axon formation. These mice may be useful in studying the role of synapsin II in neurodevelopment.

Donating Investigator

Hung-Teh Kao, Nathan Kline Institute

Paul Greengard, Rockefeller University

Genetic overview

Genetic Background	Generation

Syn2^tm1Pggd

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Syn2	synapsin II

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Research Applications

Neurobiology Research

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Details

Detailed Description

TheSyn2 gene is a member of the synapsin family of neuronal phophsoproteins, which are associated with neurotransmitter release and synaptogenesis. Synapsin proteins are associated with autism. Synapsin II localizes to presynaptic terminals. The synapsin II knockout allele has a PGK-neo cassette replacing exon 1 of the Syn2 gene. Homozygous mice exhibit decreased brain weight, impaired lamellipodia formation, abnormal neurite formation, aberrant actin filament distribution, delayed axon differentiation, altered cytoskeletal formation, and to a lesser extent than the synapsin I KO, delayed synapse formation. Beginning at two months of age, mice experience spontaneous seizures. Homozygous mice are viable and fertile with no reported reproductive deficiency.

Development

A targeting vector was designed by Dr. Paul Greengard (Rockefeller University) to
replace exon 1 of the synapsin II gene (Syn2) on chromosome 6 with a PGK-neomycin cassette. The construct was electroporated into 129-derived unspecified embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6J females to establish the colony. The resulting mice were bred with C57BL/6 wildtype mice for at least ten generations prior to sending males to The Jackson Laboratory Repository in 2015.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Ferreira A; Chin LS; Li L; Lanier LM; Kosik KS; Greengard P. 1998. Distinct roles of synapsin I and synapsin II during neuronal development. Mol Med 4(1):22-8PubMed: 9513186 MGI: J:91113

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Genetics

Syn2^tm1Pggd

Allele Symbol: Syn2^tm1Pggd

Allele Name	targeted mutation 1, Paul Greengard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Syn2^tm1Kao
Gene Symbol and Name	Syn2, synapsin II
Gene Synonym(s)
Strain of Origin	129
Chromosome	6
Molecular Note	Exon1 was replaced with a neomycin cassette inserted by homologous recombination.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Epilepsy
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Syn2^tm1Pggd/Syn2^tm1Pggd
Not Specified

behavior/neurological phenotype

seizures
- epileptic seizures in adults

nervous system phenotype

abnormal brain morphology

abnormal CNS synaptic transmission
- 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
- 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
- reduction in synaptic activity in dentate gyrus mossy cells of young pre-symptomatic mutants

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

abnormal hippocampus physiology
- 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
- Normal - however, granule cell excitability is normal
- 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

abnormal miniature excitatory postsynaptic currents
- a decrease in excitatory presynaptic input on hilar mossy cells
- 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

abnormal neuron morphology
- neurons in culture are arrested in an undifferentiated stage prior to axon formation

abnormal synaptic vesicle number
- 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

decreased brain weight
- at E16, brain weight was 17% lower than normal
- by E19 the brain weight reduction was only 12%

decreased synaptic depression
- 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

delayed CNS synapse formation
- synapse formation is delayed 2-3 days in culture

seizures
- epileptic seizures in adults

The following phenotype relates to a compound genotype created using this strain

Genotype: Syn2^tm1Pggd/Syn2^tm1Pggd
B6.1129-Syn2

behavior/neurological phenotype

abnormal emotion/affect behavior
- 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
- 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

abnormal short term object recognition memory
- erm social recognition
- 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

abnormal social investigation
- 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 resident-intruder test, mutants show reduced social interaction with the intruder mice after 1-2 months of social isolation
- 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

increased aggression towards mice
- in the social dominance tube test, adults show more dominant behavior than controls

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

mammalian phenotype

taste/olfaction phenotype
- Normal - olfaction is intact

References

Ferreira A; Chin LS; Li L; Lanier LM; Kosik KS; Greengard P. 1998. Distinct roles of synapsin I and synapsin II during neuronal development. Mol Med 4(1):22-8PubMed: 9513186 MGI: J:91113

Additional - Syn2^tm1Pggd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Syn2-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the synapsin II KO mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41437 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Questions about Terms of Use

Licensing Information

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Also Known As:synapsin II KO

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Syn2tm1Pggd

Allele Symbol: Syn2tm1Pggd

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Syn2tm1Pggd/Syn2tm1PggdNot Specified

behavior/neurological phenotype

nervous system phenotype

Genotype: Syn2tm1Pggd/Syn2tm1PggdB6.1129-Syn2

behavior/neurological phenotype

mammalian phenotype

References

Additional - Syn2tm1Pggd related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Syn2^tm1Pggd

Allele Symbol: Syn2^tm1Pggd

Genotype: Syn2^tm1Pggd/Syn2^tm1Pggd
Not Specified

Genotype: Syn2^tm1Pggd/Syn2^tm1Pggd
B6.1129-Syn2

Additional - Syn2^tm1Pggd related