Strain Name:

STOCK Shank3tm1.1Pfw/J

Stock Number:

018398

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
These Shank3(+/ΔC) mice may be useful for studying behavioral and synaptic abnormalities associated with autism spectrum disorder.

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

Former Names B6.129S6(Cg)-Shank3tm1.1Pfw/J    (Changed: 20-DEC-12 )
B6.Cg-Shank3tm1.1Pfw/J    (Changed: 10-MAY-12 )
Type Congenic; Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN?pN1
Generation Definitions
 
Donating Investigator Paul Worley,   Johns Hopkins University School of Medic

Description
These Shank3(+/ΔC) mutant mice lack exon 21 of the SH3/ankyrin domain gene 3 (Shank3) gene. The removal of exon 21 causes a frameshift which results in the production of SHANK3 protein lacking the entire C-terminal region, including the Homer-binding site in the sterile alpha motif (SAM) domain. SHANK3 is a synaptic scaffolding protein expressed in the postsynaptic density (PSD) of excitatory synapses. SHANK3 mutations have been identified in cases of intellectual disability such as autism spectrum disorder (ASD), Phelan-McDermid syndrome, and schizophrenia. Truncated SHANK3 protein associates with wildtype protein resulting in a 75% reduction in wildtype SHANK3 in cortical cultures, and 90% reduction in synaptic cultures. These Shank3(+/ΔC) mice exhibit behavioral deficits suggestive of autism, including aberrant social interactions leading to aggressive behaviors. These mice also have reduced NMDA receptor function in hippocampal neurons resulting in the reductions in long term potential and depression. Shank3(+/ΔC) mice display normal learning and memory, and show no alterations in postsynaptic density proteins, spine morphology, or synapse number. Mice that are heterozygous for this allele are viable and fertile. The donating investigator has reported some fertility issues when maintaining a homozygous colony.

Development
A targeting vector was designed to insert a loxP site upstream of exon 21 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 21 of the SH3/ankyrin domain gene 3 (Shank3) gene. The construct was electroporated into 129S6/SvEvTac embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred to C57BL/6J mice. The resulting offspring, were bred with mice expressing actin-cre to delete the neo cassette and exon 21, and progeny were crossed to remove the Cre-expressing transgene. The donating investigator reported that the resulting Shank3(ΔC) mice were bred to C57BL/6J mice for at least 5 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 18 of the 27 markers throughout the genome were found to be segregating for 129 and B6. Also, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Shank3
017889   B6(Cg)-Shank3tm1.1Bux/J
017890   B6(Cg)-Shank3tm1.2Bux/J
017688   B6.129-Shank3tm2Gfng/J
017442   B6.129S7-Shank3tm1Yhj/J
024033   B6.FVB-Tg(Shank3-EGFP)1Hzo/J
View Strains carrying other alleles of Shank3     (5 strains)

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).
Autism
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Phelan-Mcdermid Syndrome   (SHANK3)
Schizophrenia 15; SCZD15   (SHANK3)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Shank3tm1.1Pfw/Shank3+

        B6.129S6-Shank3tm1.1Pfw
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mice exhibit normal short-term spatial recognition, spatial working memory, context and cue-related fear memory and extinction, anxiety levels, and learning of motor skills   (MGI Ref ID J:198768)
    • abnormal social/conspecific interaction
      • mice exhibit reduced social investigation modulated by episodes of aggression compared with wild-type mice   (MGI Ref ID J:198768)
      • abnormal social investigation
        • mice exhibit reduced social investigation modulated by episodes of aggression compared with wild-type mice   (MGI Ref ID J:198768)
        • male mice spend more time investigating an enclosed male stimulus compared with wild-type mice   (MGI Ref ID J:198768)
        • male mice exhibit increased latency to approach a sexually receptive enclosed female mouse compared with wild-type mice   (MGI Ref ID J:198768)
        • however, mice exhibit normal social recognition memory   (MGI Ref ID J:198768)
      • increased aggression towards mice
        • mice exhibit increased aggression towards a novel stimulus mouse and in a resident-intruder tests compared with wild-type mice   (MGI Ref ID J:198768)
    • abnormal vocalization
      • male mice exhibit latency to first ultrasound call in the presence of a female mice compared with wild-type mice   (MGI Ref ID J:198768)
    • decreased startle reflex
      • mice exhibit lower amplitudes and longer latencies of startle response compared with wild-type mice   (MGI Ref ID J:198768)
    • induced hyperactivity
      • in dizocilpine- or amphetamine-treated mice   (MGI Ref ID J:198768)
      • however, mice do not exhibit novelty-induced hyperactivity   (MGI Ref ID J:198768)
  • nervous system phenotype
  • abnormal glutamate-mediated receptor currents
    • the ratio of NMDA to AMPA-dependent response in the cortex is reduced compared to in wild-type mice   (MGI Ref ID J:198768)
    • however, AMPAR-mediated miniature excitatory postsynaptic current amplitude and frequency are normal   (MGI Ref ID J:198768)
    • reduced NMDA-mediated synaptic currents   (MGI Ref ID J:198768)
  • abnormal long term depression
    • glutamate receptor long term depression (mGluR-LTD) induced by DHPG is increased and inhibited by cycloheximide compared to in wild-type mice   (MGI Ref ID J:198768)
    • LTD induced by paired-pulse low-frequency stimulation is increased compared to in wild-type mice   (MGI Ref ID J:198768)
  • decreased synaptic depression
    • NMDAR-dependent long term depression of Schaffer collateral-CA1 synapses is reduced compared to in wild-type mice   (MGI Ref ID J:198768)
  • reduced long term potentiation
    • NMDAR-dependent long term potentiation induction magnitude is reduced and decays more rapidly than in wild-type mice   (MGI Ref ID J:198768)
View Research Applications

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

Neurobiology Research
Neurodevelopmental Defects
      Autism

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Shank3tm1.1Pfw
Allele Name targeted mutation 1.1, Paul Worley
Allele Type Targeted (other)
Common Name(s) Shank3(deltaC); Shank3tm1.1Bxia;
Mutation Made By Bo Xiao,   Johns Hopkins University School of Medic
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Shank3, SH3/ankyrin domain gene 3
Chromosome 15
Gene Common Name(s) AI841104; DEL22q13.3; PROSAP2; PSAP2; SCZD15; SPANK-2; expressed sequence AI841104;
General Note The data reported for this allele were originally described in:

Bangash MA, Park JM, Melnikova T, Wang D, Jeon SK, Lee D, Syeda S, Kim J, Kouser M, Schwartz J, Cui Y, Zhao X, Speed HE, Kee SE, Tu JC, Hu JH, Petralia RS, Linden DJ, Powell CM, Savonenko A, Xiao B, Worley PF. Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism. Cell. 2011 May 27;145(5):758-72. PMID:21565394.

This paper was retracted; however, the prinicpal investigator has confirmed the validity of the data related to the molecular gene targeting and the phenotypic description of the mutant mice carrying this allele. Please see the retraction notes for further details about the data in the original paper.
Molecular Note A loxP site was inserted upstream of exon 21. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 21. Cre-mediated recombination removed exon 21 and the neo cassette. [MGI Ref ID J:198768]

Genotyping

Genotyping Information

Genotyping Protocols

Shank3tm1.1Pfw, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Shank3tm1.1Pfw related

Worley P. 2013. Haploinsufficiency of Shank3 causes Autism-like phenotypes in mice MGI Direct Data Submission :.  [MGI Ref ID J:198768]

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 maintaining a live colony, heterozygous males may be bred to wildtype females from the colony or to C57BL/6J female mice (Stock No. 000664). The donating investigator maintains this non-reciprocal cross to exclude effects of possible maternal autism spectrum disorder (ASD)-like phenotype on rearing. Some fertility issues have been reported when maintaining a homozygous colony.

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.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Important Note

The reference originally describing this allele (Cell 145:758-72) has been retracted. The donating investigator has confirmed that the basis of the retraction is not related to the identity, structure or phenotype of this exon 21 deletion mutant.

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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.
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