Strain Name:

B6;129-Syngap1tm1Rlh/J

Stock Number:

008890

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Homozygous Syngap (synaptic Ras GTPase activating protein 1 homolog (rat)) targeted mutation mice die in the first week after birth due to severe sensory deficit. Heterozygotes show partial deficits in synaptic plasticity. No gene product (protein) is detected by Western blot analysis of the brain isolated from homozygous animals.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Richard L Huganir,   Johns Hopkins University; HHMI

Description
Mice that are heterozygous for the synaptic Ras GTPase activating protein 1 homolog targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygotes die in the first week after birth due to severe sensory deficit. Heterozygotes show partial deficits in synaptic plasticity. No gene product (protein) is detected by Western blot analysis of the brain isolated from homozygous animals. This strain may be useful in studies of neurodevelopment, glutamate receptor trafficking and the induction of long-term potentiation (LTP).

Development
Exons 7 and 8 were replaced with a neomycin resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed once to C57BL/6J mice. This strain was maintained on a mixed C57BL/6J and 129 genetic background by the donating laboratory.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Schizophrenia; SCZD
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Mental Retardation, Autosomal Dominant 5; MRD5   (SYNGAP1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Syngap1tm1Rlh/Syngap1+

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • nervous system phenotype
  • reduced long term potentiation
    • long term potentiation induced by TBS was significantly decreased in the CA1 region of hippocampal slices, however there was no difference in the magnitude of long term depression   (MGI Ref ID J:97391)

Syngap1tm1Rlh/Syngap1+

        involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6J
  • behavior/neurological phenotype
  • abnormal social/conspecific interaction
    • mutants are unable to distinguish between familiar and novel conspecifics compared to wild-type mice which spend more time with the novel conspecifics   (MGI Ref ID J:194146)
    • social withdrawal
      • in a test for social isolation, mutants spend more time in the center compartment (a space that is separated from the other mice) than in ends of chamber where novel conspecifics were placed, indicating a preference for social isolation   (MGI Ref ID J:194146)
  • abnormal spatial working memory
    • although mutants are able to learn forced alteration rule in the automated eight-arm radial maze, mutants show a time-dependent decrease in nonmatching performance, indicating spatial working memory deficits   (MGI Ref ID J:194146)
  • decreased anxiety-related response
    • mutants exhibit random vectors through the open field unlike wild-type mice that primarily run around the outside chamber and spend most of the time in the corners, indicating abnormal anxiety levels   (MGI Ref ID J:194146)
    • mutants are more likely to venture into the center of the field during the first few minutes of the test session, indicating decreased thigmotaxis   (MGI Ref ID J:194146)
    • in the elevated plus maze, mutants spend less time in the closed arm and more time in the open arm compared to wild-type mice, indicating decreased anxiety levels   (MGI Ref ID J:194146)
  • hyperactivity
    • mutants exhibit elevated horizontal activity compared to wild-type littermates and this behavior is nonhabituating over repeated trials   (MGI Ref ID J:194146)
    • juvenile, newly weaned mutants also exhibit increased horizontal activity   (MGI Ref ID J:194146)
    • antipsychotic drug clozapine ameliorates the persistent hyperactivity   (MGI Ref ID J:194146)
    • the NMDAR antagonist, MK-801, has a reduced effect on hyperactivity in mutants compared to wild-type mice   (MGI Ref ID J:194146)
  • impaired cued conditioning behavior
    • mutants exhibit reduced freezing in response to a conditioning tone previously associated with a mild footshock, however the freezing response is intact as behavioral responses to a fear-associated context are normal   (MGI Ref ID J:194146)
    • activity during conditioning tone presentation is normal, however activity is elevated during tone presentation in the retrieval test   (MGI Ref ID J:194146)
  • increased horizontal stereotypic behavior
    • mutants show an increase in stereotypies in the open field test compared to wild-type littermates, most pronounced at the beginning of a 2 hour test session   (MGI Ref ID J:194146)
    • mutants show increased stereotypic behavior in 30 minute open field trials over 5 consecutive days, indicating behavior is nonhabituating   (MGI Ref ID J:194146)
  • increased startle reflex
    • mutants respond more strongly to the 120 dB stimulus then wild-type mice   (MGI Ref ID J:194146)
    • mutants show enhanced startle responses at the highest amplitudes (loudest pulses)   (MGI Ref ID J:194146)
  • nervous system phenotype
  • decreased prepulse inhibition   (MGI Ref ID J:194146)

Syngap1tm1Rlh/Syngap1tm1Rlh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • mortality/aging
  • complete postnatal lethality
    • pups die between P5 and P7   (MGI Ref ID J:97391)
  • growth/size/body phenotype
  • decreased body size
    • between P4 and P6, pups stay small in size   (MGI Ref ID J:97391)
  • behavior/neurological phenotype
  • abnormal suckling behavior
    • by P3, pups do not feed from the mother   (MGI Ref ID J:97391)
  • bradykinesia
    • by P3, homozygous mutants show less movement   (MGI Ref ID J:97391)
  • nervous system phenotype
  • abnormal neuron morphology
    • homozygotes had significantly fewer morphological silent synapses (synapses that contain NMDA receptors but not AMPA receptors) and had a greater number of AMPA receptor clusters in cortical neuronal cultures   (MGI Ref ID J:97391)
  • decreased brain size   (MGI Ref ID J:97391)

Syngap1tm1Rlh/Syngap1tm1Rlh

        involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6J
  • mortality/aging
  • complete postnatal lethality

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

Syngap1tm1Rlh/Syngap1+

        involves: 129S1/Sv * 129X1/SvJ
  • nervous system phenotype
  • *normal* nervous system phenotype
    • at P14, mice exhibit normal medial perforant path release probability and intrinsic spiking of dentate gyrus neurons   (MGI Ref ID J:193208)
    • abnormal CNS synaptic transmission
      • photosimulation-evoked signals originating in the dentate gyrus are amplified as they spread through the hippocampus unlike in wild-type mice   (MGI Ref ID J:193208)
      • synaptic transmission in the Schaeffer Collateral pathway in the CA1 is strong during early development compared with wild-type mice   (MGI Ref ID J:193208)
      • however, synaptic transmission in the Schaeffer Collateral pathway in the CA1 in adult mice is normal   (MGI Ref ID J:193208)
      • abnormal excitatory postsynaptic potential
        • by P14, field excitatory postsynaptic potential is increased compared to in control mice   (MGI Ref ID J:193208)
        • however, synaptic function at P9, P21 and later is normal   (MGI Ref ID J:193208)
      • abnormal glutamate-mediated receptor currents
        • at P14, mice exhibit an increase in the ratio of AMPA/NMDA currents in dentate gyrus granule neurons compared with wild-type mice   (MGI Ref ID J:193208)
        • however, NMDAR-evoked synaptic transmission is normal   (MGI Ref ID J:193208)
        • enhanced AMPA-mediated synaptic currents
          • increased sensitivity at P14   (MGI Ref ID J:193208)
      • abnormal miniature excitatory postsynaptic currents
        • increased amplitude and frequency at P14   (MGI Ref ID J:193208)
        • however, both are normal at P21   (MGI Ref ID J:193208)
      • abnormal miniature inhibitory postsynaptic currents
        • increased frequency and amplitude in the dentate gyrus neurons   (MGI Ref ID J:193208)
    • abnormal dendrite morphology
      • at P14, dentate gyrus neuron dendritic trees exhibit a decrease in the spatial volume compared with in wild-type mice   (MGI Ref ID J:193208)
      • abnormal dendritic spine morphology
        • larger spines by P14 and persisting into adulthood   (MGI Ref ID J:193208)
        • more mushroom-type spines and fewer stubby spines beginning in the second postnatal week   (MGI Ref ID J:193208)
        • spines are less motile at P14   (MGI Ref ID J:193208)
        • some spines exhibit a spontaneous increase in head volume   (MGI Ref ID J:193208)
        • however, spine density is normal   (MGI Ref ID J:193208)
    • audiogenic seizures   (MGI Ref ID J:193208)
    • increased susceptibility to pharmacologically induced seizures
      • fluorothyl-induced   (MGI Ref ID J:193208)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mice exhibit normal contextual fear memory   (MGI Ref ID J:193208)
    • abnormal discrimination learning
      • mice are unable to discriminate between two contexts during contextual fear training unlike wild-type mice   (MGI Ref ID J:193208)
    • audiogenic seizures   (MGI Ref ID J:193208)
    • hyperactivity
      • in an open field at P14   (MGI Ref ID J:193208)
    • increased susceptibility to pharmacologically induced seizures
      • fluorothyl-induced   (MGI Ref ID J:193208)
View Research Applications

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

Developmental Biology Research
Postnatal Lethality
      Homozygous

Neurobiology Research
Neurodevelopmental Defects
Receptor Defects
      glutamate receptor: NMDA

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Syngap1tm1Rlh
Allele Name targeted mutation 1, Richard L Huganir
Allele Type Targeted (knock-out)
Mutation Made By Richard Huganir,   Johns Hopkins University; HHMI
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Syngap1, synaptic Ras GTPase activating protein 1 homolog (rat)
Chromosome 17
Gene Common Name(s) Gm1963; MRD5; RASA1; RASA5; SYNGAP; gene model 1963, (NCBI);
Molecular Note To eliminate all possible splice variants, exon 7, which contains the first common methionine present in the shortest splice variant, as well as exon 8, which encodes part of the C2 domain, were replaced with a neomycin resistance gene placed in the opposite orientation. Immunoblot of brain homogenates at P5 demonstrated that protein is abolished in mutants. Overexposure of the immunoblot showed a smear present at less than 2% of wild-type levels, likely made up of protein products resulting from cryptic start sites downstream of the deleted sequence. [MGI Ref ID J:97391]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kim JH; Lee HK; Takamiya K; Huganir RL. 2003. The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity. J Neurosci 23(4):1119-24. [PubMed: 12598599]  [MGI Ref ID J:97391]

Additional References

Syngap1tm1Rlh related

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):709-23. [PubMed: 23141534]  [MGI Ref ID J:193208]

Clement JP; Ozkan ED; Aceti M; Miller CA; Rumbaugh G. 2013. SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity. J Neurosci 33(25):10447-52. [PubMed: 23785156]  [MGI Ref ID J:199642]

Guo X; Hamilton PJ; Reish NJ; Sweatt JD; Miller CA; Rumbaugh G. 2009. Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia. Neuropsychopharmacology 34(7):1659-72. [PubMed: 19145222]  [MGI Ref ID J:194146]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Homozygotes die within a week of birth. Backcrossing further to C57BL/6 may reduce viability even more.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

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