Strain Name:

B6(Cg)-Shank3tm1.2Bux/J

Stock Number:

017890

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Availability:

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These mutant mice harbor a deletion of the SH3/ankyrin domain gene 3 (Shank3) ankyrin repeat domains (exons 4-9); this deletion prevents full-length Shank3 expression. As Shank3 is necessary for forming functional glutamatergic synapses between receptors and cytoskeletal/scaffolding elements, these mice may be useful for studying synaptic glutamate receptor development/function, transmission and plasticity, as well as Shank3 haploinsufficiency, neurobehavioral manifestations of 22q13 deletion syndrome and/or autism spectrum disorders.

Description

Strain Information

Type Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemWild-type x Heterozygote         (Female x Male)   05-FEB-13
Mating SystemHeterozygote x Wild-type         (Female x Male)   05-FEB-13
Specieslaboratory mouse
GenerationN4 (11-NOV-13)
Generation Definitions
 
Donating Investigator Joseph D Buxbaum,   Mount Sinai School of Medicine

Description
These mutant mice harbor a deletion of the SH3/ankyrin domain gene 3 ankyrin repeat domains (exons 4-9). This deletion prevents full-length Shank3 expression; Shank3 mRNA/protein is absent in homozygous postsynaptic density (PSD) fractions, and reduced 50% in heterozygous PSD fractions. Heterozygous mice are viable and fertile with no observed gross brain structure defects or seizures. Heterozygous mice exhibit reduced basal neurotransmission. Heterozygous males display less social sniffing and emit fewer ultrasonic vocalizations during interactions with estrus female mice. Following theta-burst pairing (coincident pre- and postsynaptic stimulation), heterozygous mice have impaired long-term potentiation and altered spine remodeling. Homozygous mice are viable with subtle motor abnormalities. The complete phenotype of homozygous mice is not yet characterized to date (April 2012).

Development
A targeting vector was designed to insert a loxP site upstream of exon 4, and an frt-flanked selection (neo) cassette followed by a second loxP site all downstream of exon 9 of the targeted gene. The construct was electroporated into B6.Cg-Thy1a-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric males were bred with C57BL/6NTac females to establish the colony. Next, mutant mice were bred with FLP-expressing mice (undisclosed genetic background) to remove the frt-flanked PGK-neo cassette. The resulting Shank3flox ex4-9 mice were subsequently bred to C57BL/6-congenic mice expressing Cre recombinase in embryonic tissues (CMV-Cre; see Stock No. 006054). The resulting mice with pan deletion of the Shank3 ankyrin repeat domains were obtained. These mice were then bred to C57BL/6NTac for two-to-three generations (and the Cre recombinase gene was removed) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish The Jackson Laboratory Repository colony. Of note, while backcrossing the donating investigator did not assay their colony at the Thy1 locus. As such, these mice may be segregating for the NZB-derived Thy1a allele (from Bruce4 ES cells) or the C57BL/6-derived Thy1b allele.

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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 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 mixed C57BL/6J ; 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
017688   B6.129-Shank3tm2Gfng/J
017442   B6.129S7-Shank3tm1Yhj/J
024033   B6.FVB-Tg(Shank3-EGFP)1Hzo/J
018398   STOCK Shank3tm1.1Pfw/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

Shank3tm1.2Bux/Shank3+

        C57BL/6-Shank3tm1.2Bux
  • nervous system phenotype
  • abnormal neuron physiology
    • spine enlargement accompanying long term potentiation is impaired   (MGI Ref ID J:175320)
  • abnormal synaptic transmission
    • decrease in the paired pulse ratio   (MGI Ref ID J:175320)
    • abnormal excitatory postsynaptic potential
      • reduction in the I/O curves of field excitatory postsynaptic potentials in hippocampal slices from 3-4 week old mice   (MGI Ref ID J:175320)
      • decrease in AMPA receptor mediated field potentials   (MGI Ref ID J:175320)
    • abnormal miniature excitatory postsynaptic currents
      • significantly higher frequency of miniature excitatory postsynaptic currents   (MGI Ref ID J:175320)
    • reduced long term potentiation
      • initial expression of LTP is normal but maintenance is impaired   (MGI Ref ID J:175320)
  • behavior/neurological phenotype
  • abnormal social investigation
    • total social sniffing by the males is lower   (MGI Ref ID J:175320)
    • however, no defect in olfactory abilities are detected   (MGI Ref ID J:175320)
  • abnormal vocalization
    • fewer ultrasonic vocalizations emitted during male-female social interactions session   (MGI Ref ID J:175320)

Shank3tm1.2Bux/Shank3+

        B6N.Cg-Shank3tm1.2Bux
  • behavior/neurological phenotype
  • hypoactivity
    • mice travel less in the center of the open field test during last 10 minutes of test as compared to littermate controls   (MGI Ref ID J:206790)

Shank3tm1.2Bux/Shank3tm1.2Bux

        B6N.Cg-Shank3tm1.2Bux
  • mortality/aging
  • partial lethality
    • fewer than expected homozygotes (21%) were produced from a heterozygote x heterozygote cross   (MGI Ref ID J:206790)
    • homozygote lethality is background dependent, the greatest loss is observed on the 129S6 background, followed by FVB/N and C57BL/6   (MGI Ref ID J:206790)
  • behavior/neurological phenotype
  • abnormal response to novel object
    • homozygous mice exhibit a preference for the unfamiliar mouse over the familiar mouse relative to littermate controls   (MGI Ref ID J:206790)
  • decreased anxiety-related response
    • mice are more active in elevated zero maze as determined by increases in total moving distance and total moving time   (MGI Ref ID J:206790)
    • open arc entries are increased in elevated zero-maze   (MGI Ref ID J:206790)
  • decreased vertical activity
    • decreased number of rears in open field test as compared to littermate controls   (MGI Ref ID J:206790)
  • hypoactivity
    • mice travel less in center of the open field test during first 10 minutes of test   (MGI Ref ID J:206790)
  • hyporesponsive to tactile stimuli
    • mice exhibit a longer tail flick latency in the first trial of the tail-flick assay for pain sensitivity as compared to littermate controls and mice on the FVB/N and 129S6/SvEvTac backgrounds   (MGI Ref ID J:206790)
  • impaired coordination
    • mice exhibit a lower latency to start crossing and spent a shorter time crossing in beam walking test as compared to littermate controls   (MGI Ref ID J:206790)
  • integument phenotype
  • hyporesponsive to tactile stimuli
    • mice exhibit a longer tail flick latency in the first trial of the tail-flick assay for pain sensitivity as compared to littermate controls and mice on the FVB/N and 129S6/SvEvTac backgrounds   (MGI Ref ID J:206790)
  • growth/size/body phenotype
  • decreased body weight
    • mice exhibit lower body weight than controls   (MGI Ref ID J:206790)

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

Shank3tm1.2Bux/Shank3+

        129S6.B6(Cg)-Shank3tm1.2Bux
  • behavior/neurological phenotype
  • decreased anxiety-related response
    • open arc entries are increased in elevated zero-maze as compared to littermate controls   (MGI Ref ID J:206790)
  • hyperactivity
    • mice exhibit hyperactivity in first 10 minutes of open field test, but return to activity level similar to controls   (MGI Ref ID J:206790)
  • impaired coordination
    • fewer mice were able to cross beam due to freezing/falls as compared to littermate controls   (MGI Ref ID J:206790)
  • increased thigmotaxis   (MGI Ref ID J:206790)

Shank3tm1.2Bux/Shank3tm1.2Bux

        FVB.B6(Cg)-Shank3tm1.2Bux
  • mortality/aging
  • partial lethality
    • fewer than expected homozygotes (17.71%) were produced from a heterozygote x heterozygote cross   (MGI Ref ID J:206790)
    • homozygote lethality is background dependent, the greatest loss is observed on the 129S6 background, followed by FVB/N and C57BL/6   (MGI Ref ID J:206790)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • tail flick latency is observed in mice on the C57BL/6 background, but not on FVB/N or 129S6/SvEvTac backgrounds   (MGI Ref ID J:206790)
    • abnormal response to novel object
      • homozygous mice exhibit a preference for the unfamiliar mouse rather than the familiar mouse as compared to littermate controls   (MGI Ref ID J:206790)
    • decreased anxiety-related response
      • mice are more active in elevated zero maze as determined by increases in total moving distance and total moving time   (MGI Ref ID J:206790)
      • time spent in open arc entries is increased and in closed arcs decreased in elevated zero-maze   (MGI Ref ID J:206790)
    • increased vertical activity
      • increased number of rears in open field test as compared to littermate controls   (MGI Ref ID J:206790)
  • growth/size/body phenotype
  • decreased body weight
    • mice exhibit lower body weight than controls   (MGI Ref ID J:206790)

Shank3tm1.2Bux/Shank3tm1.2Bux

        129S6.B6(Cg)-Shank3tm1.2Bux
  • mortality/aging
  • partial lethality
    • fewer than expected homozygotes (16.22%) were produced from a heterozygote x heterozygote cross   (MGI Ref ID J:206790)
    • homozygote lethality is background dependent, the greatest loss is observed on the 129S6 background, followed by FVB/N and C57BL/6   (MGI Ref ID J:206790)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • tail flick latency is observed in mice on the C57BL/6 background, but not on FVB/N or 129S6/SvEvTac backgrounds   (MGI Ref ID J:206790)
    • abnormal conditioned emotional response
      • decreased freezing is observed following 3 tone-shock associations and after third association, however no significant differences are observed in contextual or cued conditioning tests   (MGI Ref ID J:206790)
    • decreased anxiety-related response
      • open arc entries are increased in elevated zero-maze as compared to littermate controls   (MGI Ref ID J:206790)
    • decreased grip strength
      • mice exhibit decrease in mean forelimb grip strength as compared to littermate controls   (MGI Ref ID J:206790)
    • hyperactivity
      • mice exhibit hyperactivity in first 10 minutes of open field test, but return to activity level similar to controls   (MGI Ref ID J:206790)
  • growth/size/body phenotype
  • decreased body weight
    • mice exhibit lower body weight than controls   (MGI Ref ID J:206790)
View Research Applications

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

Cell Biology Research
Channel and Transporter Defects

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

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
      Tissue/Cell Markers: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Shank3tm1.2Bux
Allele Name targeted mutation 1.2, Joseph D Buxbaum
Allele Type Targeted (knock-out)
Mutation Made By Joseph Buxbaum,   Mount Sinai School of Medicine
Strain of OriginB6.Cg-Thy1
Gene Symbol and Name Shank3, SH3/ankyrin domain gene 3
Chromosome 15
Gene Common Name(s) AI841104; ProSAP2; expressed sequence AI841104;
Molecular Note A loxP site was inserted upstream of exon 4 and an FRT flanked neo cassette and second loxP site were inserted downstream of exon 9 via homologous recombination. Flp mediated recombination removed the neo cassette. Cre mediated recombination removed exons 4 - 9. Quantitative PCR and immunoblot analysis confirmed the absence of mRNA and protein expression in homozygous mice. [MGI Ref ID J:175320]

Genotyping

Genotyping Information

Genotyping Protocols

Shank3tm1.2Bux ,

Separated MCA


Tg(ACTFLPe), High Resolution Melting
Tg(ACTFLPe), Standard PCR
Shank3tm1.2Bux, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bozdagi O; Sakurai T; Papapetrou D; Wang X; Dickstein DL; Takahashi N; Kajiwara Y; Yang M; Katz AM; Scattoni ML; Harris MJ; Saxena R; Silverman JL; Crawley JN; Zhou Q; Hof PR; Buxbaum JD. 2010. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 1(1):15. [PubMed: 21167025]  [MGI Ref ID J:175320]

Additional References

Shank3tm1.2Bux related

Drapeau E; Dorr NP; Elder GA; Buxbaum JD. 2014. Absence of strong strain effects in behavioral analyses of Shank3-deficient mice. Dis Model Mech :. [PubMed: 24652766]  [MGI Ref ID J:206790]

Jiang YH; Ehlers MD. 2013. Modeling autism by SHANK gene mutations in mice. Neuron 78(1):8-27. [PubMed: 23583105]  [MGI Ref ID J:197901]

Yang M; Bozdagi O; Scattoni ML; Wohr M; Roullet FI; Katz AM; Abrams DN; Kalikhman D; Simon H; Woldeyohannes L; Zhang JY; Harris MJ; Saxena R; Silverman JL; Buxbaum JD; Crawley JN. 2012. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 32(19):6525-41. [PubMed: 22573675]  [MGI Ref ID J:184855]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryHeterozygous males display less social sniffing and emit fewer ultrasonic vocalizations during interactions with estrus female mice. Therefore when maintaining a live colony, heterozygous females may be bred with wildtype males from the colony or with C57BL/6J inbred males (Stock No. 000664).
Mating SystemWild-type x Heterozygote         (Female x Male)   05-FEB-13
Heterozygote x Wild-type         (Female x Male)   05-FEB-13
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Shank3tm1.2Bux  
Price per Pair (US dollars $)Pair Genotype
$302.00Heterozygous for Shank3tm1.2Bux x Wild-type for Shank3tm1.2Bux  
$302.00Wild-type for Shank3tm1.2Bux x Heterozygous for Shank3tm1.2Bux  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Shank3tm1.2Bux  
Price per Pair (US dollars $)Pair Genotype
$392.60Heterozygous for Shank3tm1.2Bux x Wild-type for Shank3tm1.2Bux  
$392.60Wild-type for Shank3tm1.2Bux x Heterozygous for Shank3tm1.2Bux  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

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

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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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