Overview

Also Known As:SYNGAP1^fl

The SYNGAP1^fl floxed allele has loxP sites flanking exons 6-7 of the synaptic RasGAP (SynGAP) gene. Removal of the floxed sequence disrupts expression of full-length SynGAP and results in expression of a truncated/inactive SynGAP protein. These mice may be useful in Cre-lox studies of synapse development (specifically in dendritic spine), cognitive and behavioral maturation, intellectual disability and autism spectrum disorder.

Donating Investigator

Gavin Rumbaugh, The Scripps Research Institute

Genetic overview

Genetic Background	Generation

Syngap1^tm1.1Geno

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Syngap1	synaptic Ras GTPase activating protein 1 homolog (rat)

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Research Applications

Neurobiology Research
Research Tools
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mutations that cause intellectual disability (ID) and autism spectrum disorder (ASD) are commonly found in genes that encode for synaptic proteins. Syngap1 encodes a synaptic RasGAP (SynGAP) that is largely localized to dendritic spines in neocortical pyramidal neurons, where it suppresses signaling pathways linked to NMDA receptor (NMDAR)-mediated synaptic plasticity and AMPA receptor (AMPAR) membrane insertion. Syngap1 has alternative transcriptional start sites and several alternatively spliced C-terminal exons that result in many possible SynGAP isoforms. Human SYNGAP1 haploinsufficiency results from a truncation of the full-length protein. Exon 7 contains the first common methionine present in the shortest splice variant.

The SYNGAP1^fl allele has loxP sites flanking exons 6-7 of the Syngap1 gene. Mice homozygous for the SYNGAP1^fl allele are viable and fertile with no reported abnormalities. When bred to mice that express Cre recombinase, the resulting offspring may be useful in generating tissue-specific disruption of full-length SynGAP and expression of a truncated/inactive SynGAP protein.
For example, when SYNGAP1^fl are bred to germline Cre-expressing mice, the resulting heterozygous offspring express a SynGAP protein truncated after exon 5 (known to be an inactivate SynGAP protein), as well as diminished levels of functional SynGAP (from the wildtype allele). Therefore, the heterozygous phenotype is the same as mice heterozygous for the global knockout allele, and both are a model of human SYNGAP1 haploinsufficiency - exhibiting normal synaptic transmission, modest defects in synaptic plasticity, enhanced synaptic function (accelerated rate of glutamatergic synapse maturation) during early neural development and profound cognitive and behavioral abnormalities. Specifically, heterozygous SynGAP-deficiency significantly disrupts excitatory/inhibitory (E/I) balance in the neural networks that support cognition and behavior. Abnormal behavioral phenotypes can be observing as early as 21 days of age with ~100% penetrance (although physiological abnormalities can be measured even earlier through other methods such as electrophysiological recordings). Furthermore, mice homozygous for the germline deletion of exons 6-7 are phenotypically the same as global knockout homozygotes - exhibiting complete postnatal lethality between 2-5 days of age.
In addition, to explore the behavioral contribution of in vivo Syngap1 dysfunction in distinct cellular populations, SYNGAP1^fl mice may be bred to Emx1^{IRES cre} mice (forebrain glutamatergic neurons and glia; Stock No. 005628), Gad2-IRES-Cre mice (developing GABAergic neurons; see Stock Nos. 010802 / 028867) and/or PV-Cre mice (parvalbumin-positive neurons; see Stock Nos. 008069 / 017320).

Development

The conditional SYNGAP1 knockout mouse line (SYNGAP1^fl) was constructed by genOway S.A. (France) as a pay-for-service on behalf of Dr. Gavin Rumbaugh (The Scripps Research Institute).
The targeting vector was designed to insert a loxP site upstream of exon 6, and a frt-flanked neo cassette followed by a second loxP site just downstream of exon 7 of the synaptic Ras GTPase activating protein 1 homolog (rat) locus (Syngap1) on chromosome 17.

The construct was electroporated into 129S2/SvPas-derived embryonic stem (ES) cells. Correctly targeted ES cells were identified and injected into recipient blastocysts. The donating investigator reports that chimeric males were bred Flp-deleter females (on a C57BL/6J genetic background) for germline deletion of the neo cassette; resulting in mice with the "Neo- SynGAP1 Flox" allele (SYNGAP1^fl).

The SYNGAP1^fl colony was maintained on this mixed genetic background for several generations (and the Flp-expressing allele was removed) prior to sending males (with black or agouti coat color) to The Jackson Laboratory Repository in 2012.

Upon arrival, males were used to cryopreserve sperm. To establish a living mouse colony, an aliquot of the frozen sperm may be used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Control Suggestions

None Available

Additional Information

Considerations for Choosing Controls

Selected References

Clement JP; Aceti M; Creson TK; Ozkan ED; Shi Y; Reish NJ; Almonte AG; Miller BH; Wiltgen BJ; Miller CA; Xu X; Rumbaugh G. 2012. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses. Cell 151(4):709-23PubMed: 23141534 MGI: J:193208

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Genetics

Syngap1^tm1.1Geno

Allele Symbol: Syngap1^tm1.1Geno

Allele Name	targeted mutation 1.1, Genoway
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Syngap1^tm1.1Geno; targeted mutation 1.1, Genoway
Gene Symbol and Name	Syngap1, synaptic Ras GTPase activating protein 1 homolog (rat)
Gene Synonym(s)	RASA1; RASA5; SYNGAP; gene model 1963, (NCBI); MRD5; Gm1963; Syngap
Strain of Origin	129S2/SvPas
Chromosome	17
Molecular Note	A loxP site was inserted usptream of exon 6. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 7. Flp-mediated recombination removed the neo cassette and left exons 6 and 7 floxed.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Neurodevelopmental Defects
  - Autism
- Behavioral and Learning Defects
- Channel and Transporter Defects
  - calcium: glutamate receptor
- Receptor Defects
  - glutamate receptor: NMDA
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Cre-lox System
  - loxP-flanked Sequences
Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

References

Clement JP; Aceti M; Creson TK; Ozkan ED; Shi Y; Reish NJ; Almonte AG; Miller BH; Wiltgen BJ; Miller CA; Xu X; Rumbaugh G. 2012. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses. Cell 151(4):709-23PubMed: 23141534 MGI: J:193208

Additional - Syngap1^tm1.1Geno related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Syngap1
- Genotyping resources and troubleshooting
Breeding Considerations

Mice homozygous for the floxed allele are viable and fertile with no reported abnormalities. When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Alternatively, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the SYNGAP1^fl mouse strain in a publication, please cite the originating article(s) and include JAX stock #029303 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Syngap1<tm1.1Geno>

Related Products and Services

Frozen Mouse Embryo	STOCK Syngap1<tm1.1Geno>/RumbJ	$2595.00
Frozen Mouse Embryo	STOCK Syngap1<tm1.1Geno>/RumbJ	$2595.00
Frozen Mouse Embryo	STOCK Syngap1<tm1.1Geno>/RumbJ	$3373.50
Frozen Mouse Embryo	STOCK Syngap1<tm1.1Geno>/RumbJ	$3373.50

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Also Known As:SYNGAP1fl

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Syngap1tm1.1Geno

Allele Symbol: Syngap1tm1.1Geno

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Syngap1tm1.1Geno 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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

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

Also Known As:SYNGAP1^fl

Syngap1^tm1.1Geno

Allele Symbol: Syngap1^tm1.1Geno

Additional - Syngap1^tm1.1Geno related