Overview

Also Known As:Syn 1 KO

Homozygous synapsin I knockout mice exhibit seizures, delayed axonal outgrowth and delayed synapse formation. These mice may be useful in studying the role of synapsin I in neurodevelopment.

Donating Investigator

Hung-Teh Kao, Nathan Kline Institute

Paul Greengard, Rockefeller University

Genetic overview

Genetic Background	Generation

Syn1^tm1Pggd

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Syn1	synapsin I

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Research Applications

Neurobiology Research

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Details

Detailed Description

Syn1, the most abundant member of the synapsin family of neuronal phophoproteins, is associated with neurotransmitter release and synaptogenesis. Synapsin I localizes to presynaptic terminals. Synapsin proteins are associated with autism. The synapsin I knockout allele has a PGK-neo cassette replacing exon 1 of the Syn1 gene. Homozygous mice exhibit a delay in the outgrowth of presynaptic neurites, axonal elongation and synapse formation in hippocampal neurons. 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 I gene (Syn1) on chromosome X with a PGK-neomycin cassette. The construct was electroporated into 129P2/OlaHsd-derived E14 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

Chin LS; Li L; Ferreira A; Kosik KS; Greengard P. 1995. Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proc Natl Acad Sci U S A 92(20):9230-4PubMed: 7568107 MGI: J:29085

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Genetics

Syn1^tm1Pggd

Allele Symbol: Syn1^tm1Pggd

Allele Name	targeted mutation 1, Paul Greengard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Syn1^tm1Lli; SynI^-
Gene Symbol and Name	Syn1, synapsin I
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	X
Molecular Note	Exon 1 was replaced by a neomycin selection cassette inserted by homologous recombination. Western blot analysis of homozygous mutant brain tissues indicated an absence of both protein isoforms, Synapsin Ia and Synapsin Ib, produced by the endogenous locus.

Disease/Phenotype

Disease Terms

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

autism spectrum disorder

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: Syn1^tm1Pggd/Syn1^tm1Pggd
involves: 129

behavior/neurological phenotype

abnormal seizure response to electrical stimulation
- electrical stimulation to the amygdala resulted in clonic seizures of longer duration and intensity than controls

nervous system phenotype

abnormal excitatory postsynaptic potential
- recovery of synaptic transmission from tetanic stimulation was delayed

abnormal hippocampus pyramidal cell morphology
- retarded growth of predendritic neurites and axons was observed in vitro

abnormal neurotransmitter secretion
- release of glutamate from synaptosomes purified from the cerebral cortex was impaired; impairment may be due to lack of synaptic vesicle clustering at presynaptic terminals

abnormal seizure response to electrical stimulation
- electrical stimulation to the amygdala resulted in clonic seizures of longer duration and intensity than controls

abnormal synaptic vesicle clustering
- there is lack of synaptic vesicle clustering at presynaptic terminals

delayed CNS synapse formation
- observed in hippocampal neurons in culture

increased synaptic depression

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

Genotype: Syn1^tm1Pggd/Syn1^tm1Pggd
B6.129P2-Syn1

behavior/neurological phenotype

abnormal emotion/affect behavior
- after habituation to marbles, mutants still bury less marbles than controls, suggesting this behavior is not due to an altered response to novelty but a decrease in interest toward the environment
- Normal - 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 social investigation
- in the resident-intruder test, mutants show reduced social interaction with the intruder mice after 1-2 months of social isolation

impaired social transmission of food preference
- in the social transmission of food preference task, mutants show an absence of preference for the cued food over the novel food after one hour after social interaction with the demonstrator cagemate

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

mammalian phenotype

taste/olfaction phenotype
- Normal - olfaction is intact

References

Chin LS; Li L; Ferreira A; Kosik KS; Greengard P. 1995. Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proc Natl Acad Sci U S A 92(20):9230-4PubMed: 7568107 MGI: J:29085

Additional - Syn1^tm1Pggd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Syn1 alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Hemizygote
Citation
When using the Syn 1 KO mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41436 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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

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Also Known As:Syn 1 KO

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Syn1tm1Pggd

Allele Symbol: Syn1tm1Pggd

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: Syn1tm1Pggd/Syn1tm1Pggdinvolves: 129

behavior/neurological phenotype

nervous system phenotype

Genotype: Syn1tm1Pggd/Syn1tm1PggdB6.129P2-Syn1

behavior/neurological phenotype

mammalian phenotype

References

Additional - Syn1tm1Pggd related

Genotyping Protocols

Breeding Considerations

Mating System

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

Syn1^tm1Pggd

Allele Symbol: Syn1^tm1Pggd

Genotype: Syn1^tm1Pggd/Syn1^tm1Pggd
involves: 129

Genotype: Syn1^tm1Pggd/Syn1^tm1Pggd
B6.129P2-Syn1

Additional - Syn1^tm1Pggd related