Strain Name:

B6.129-Shank3tm2Gfng/J

Stock Number:

017688

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Availability:

Repository- Live

The Shank3B- knockout allele has a neo cassette replacing exons 13-16 (PDZ domain) of the SH3/ankyrin domain gene 3 locus, resulting altered expression of the Shank3b isoform. These mice may be useful for studying behavioral abnormalities associated with autism spectrum disorder.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHeterozygote x C57BL/6J (000664)         (Female x Male)   08-FEB-13
Mating SystemC57BL/6J (000664) x Heterozygote         (Female x Male)   08-FEB-13
Specieslaboratory mouse
GenerationF5+N4 (07-FEB-14)
Generation Definitions
 
Donating Investigator Guoping Feng,   Massachusetts Institute of Technology

Description
SHANK3 is a synaptic scaffolding protein, expressed in the postsynaptic density (PSD) of excitatory synapses. Five intragenic promoters exist, allowing for extensive alternative splicing. SHANK3 mutations have been identified in cases of intellectual disability such as autism spectrum disorder (ASD), Phelan-McDermid syndrome, and Schizophrenia. In this strain a neo cassette replaces exons 13-16 of the Shank3 gene. Specifically, the PDZ domain is disrupted resulting in a deficiency of Shank3α and Shank3β, and a reduction in expression of the Shank3γ isoform. Mice display abnormal social behaviors, excessive grooming, and self-injurious repetitive behaviors. Shank3b-/- mice also exhibit defects at striatal synapses and cortical-striatal circuits, as well as changes in medium spiny neuron morphology and density. Homozygotes are viable and fertile. These mice may be useful for studying behavioral abnormalities associated with ASD.

Development
A targeting vector was designed to replace exons 13-16 of SH3/ankyrin domain 3 (Shank3) gene with a neomycin resistance (neo) 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 C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6J females. These Shank3b mice were then intercrossed for five generations and maintained on a mixed C57BL/6J x 129 background prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were additionally backcrossed to C57BL/6J inbred mice (Stock No. 000664) using a marker-assisted, speed congenic approach to establish this congenic line.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Shank3
017889   B6(Cg)-Shank3tm1.1Bux/J
017890   B6(Cg)-Shank3tm1.2Bux/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

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

Shank3tm2Gfng/Shank3tm2Gfng

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mice exhibit normal learning and memory in a Morris water maze   (MGI Ref ID J:171113)
    • decreased vertical activity   (MGI Ref ID J:171113)
    • environmentally induced seizures
      • mice occasionally exhibit handling-induced seizures unlike wild-type mice   (MGI Ref ID J:171113)
      • however, no spontaneous seizures are observed   (MGI Ref ID J:171113)
    • increased anxiety-related response
      • mice exhibit less time exploring the open arms of an elevated plus maze compared with wild-type mice   (MGI Ref ID J:171113)
      • mice exhibit increased latency to crossing a bright area in a light-dark emergence test compared with wild-type mice   (MGI Ref ID J:171113)
      • however, mice exhibit normal thigmotaxis in an open field and time spent on either side of the box in the light-dark emergence test   (MGI Ref ID J:171113)
    • increased grooming behavior
      • resulting in skin lesions   (MGI Ref ID J:171113)
    • social withdrawal
      • mice prefer to interact with an empty cage rather than a social partner unlike wild-type mice   (MGI Ref ID J:171113)
      • mice spend less time interacting with a social partner than wild-type mice   (MGI Ref ID J:171113)
      • mice fail to spend more time with a novel social partner unlike wild-type mice   (MGI Ref ID J:171113)
      • social withdrawal is not alleviated by cross fostering pups with wild-type dams   (MGI Ref ID J:171113)
  • nervous system phenotype
  • abnormal miniature excitatory postsynaptic currents
    • reduced frequency and peak amplitude in medium spiny neurons   (MGI Ref ID J:171113)
    • however, miniature excitatory postsynaptic current frequency and amplitude in the hippocampal CA1 sub-region are normal   (MGI Ref ID J:171113)
  • abnormal striatum morphology
    • mice exhibit striatal hypertrophy compared with wild-type mice   (MGI Ref ID J:171113)
    • abnormal medium spiny neuron morphology
      • medium spiny neurons exhibit neuronal hypertrophy with increased complexity of dendritic arborization, total dendritic length, and surface area compared to in wild-type mice   (MGI Ref ID J:171113)
      • spine density is reduced compared to in wild-type mice   (MGI Ref ID J:171113)
      • the neck width of medium spiny neuron spines is slightly larger than in wild-type mice   (MGI Ref ID J:171113)
  • abnormal synapse morphology
    • mice exhibit abnormal post-synaptic density composition compared to in wild-type mice   (MGI Ref ID J:171113)
  • environmentally induced seizures
    • mice occasionally exhibit handling-induced seizures unlike wild-type mice   (MGI Ref ID J:171113)
    • however, no spontaneous seizures are observed   (MGI Ref ID J:171113)
  • integument phenotype
  • skin lesions
    • at 3 to 6 months of age, mice exhibit pronounced skin lesions with varying degrees of penetrance due to excessive self-grooming unlike wild-type mice   (MGI Ref ID J:171113)
View Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Neurodevelopmental Defects
      Autism

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Shank3tm2Gfng
Allele Name targeted mutation 2, Guoping Feng
Allele Type Targeted
Common Name(s) Shank3B-;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
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;
Molecular Note The sequence from exons 13 through 16, which encode the PDZ domain, was replaced with a neo cassette. The absence of alpha and beta isoform expression and reduced gamma isoform expression were confirmed by western blot analysis on brain extracts. [MGI Ref ID J:171113]

Genotyping

Genotyping Information

Genotyping Protocols

Shank3tm2Gfng-Alternate 2,

SEPARATED MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Peca J; Feliciano C; Ting JT; Wang W; Wells MF; Venkatraman TN; Lascola CD; Fu Z; Feng G. 2011. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472(7344):437-42. [PubMed: 21423165]  [MGI Ref ID J:171113]

Additional References

Shank3tm2Gfng related

Han K; Holder Jr JL; Schaaf CP; Lu H; Chen H; Kang H; Tang J; Wu Z; Hao S; Cheung SW; Yu P; Sun H; Breman AM; Patel A; Lu HC; Zoghbi HY. 2013. SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties. Nature :. [PubMed: 24153177]  [MGI Ref ID J:201867]

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]

Olexova L; Talarovicova A; Lewis-Evans B; Borbelyova V; Krskova L. 2012. Animal models of autism with a particular focus on the neural basis of changes in social behaviour: an update article. Neurosci Res 74(3-4):184-94. [PubMed: 23142422]  [MGI Ref ID J:192363]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryMutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) using a marker-assisted, speed congenic approach to establish this congenic line. When maintaining the live congenic colony, homozygous mice may be bred together. If breeding homozygous mice, note that homozygous mice exhibit excessive grooming that result in skin lesions.
Mating SystemHeterozygote x C57BL/6J (000664)         (Female x Male)   08-FEB-13
C57BL/6J (000664) x Heterozygote         (Female x Male)   08-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 Shank3tm2Gfng  
Price per Pair (US dollars $)Pair Genotype
$304.00Heterozygous for Shank3tm2Gfng x Wild-type for Shank3tm2Gfng  
$304.00Wild-type for Shank3tm2Gfng x Heterozygous for Shank3tm2Gfng  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

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 Shank3tm2Gfng  
Price per Pair (US dollars $)Pair Genotype
$395.20Heterozygous for Shank3tm2Gfng x Wild-type for Shank3tm2Gfng  
$395.20Wild-type for Shank3tm2Gfng x Heterozygous for Shank3tm2Gfng  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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