Overview

Also Known As:Shank3B^-

The Shank3B- knockout allele has a neo cassette replacing the PDZ domain (exons 13-16) of the Shank3 gene, resulting altered expression of the Shank3b isoform. These mice may be useful for studying behavioral abnormalities associated with autism spectrum disorder.

Donating Investigator

Guoping Feng, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation
	F5+N6F1 (2019-03-01 00:00:00)

Shank3^tm2Gfng

Allele Type	Gene Symbol	Gene Name
Targeted	Shank3	SH3 and multiple ankyrin repeat domains 3

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

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Details

Detailed 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 Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):437-42PubMed: 21423165 MGI: J:171113

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Genetics

Shank3^tm2Gfng

Allele Symbol: Shank3^tm2Gfng

Allele Name	targeted mutation 2, Guoping Feng
Allele Type	Targeted
Allele Synonym(s)	Shank3/F; Shank3B^-
Gene Symbol and Name	Shank3, SH3 and multiple ankyrin repeat domains 3
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	15
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.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Phelan-McDermid syndrome

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

autism spectrum disorder

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Shank3^tm2Gfng/Shank3^tm2Gfng
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

decreased vertical activity

environmentally induced seizures
- Normal - however, no spontaneous seizures are observed
- mice occasionally exhibit handling-induced seizures unlike wild-type mice

increased anxiety-related response
- Normal - however, mice exhibit normal thigmotaxis in an open field and time spent on either side of the box in the light-dark emergence test
- mice exhibit increased latency to crossing a bright area in a light-dark emergence test compared with wild-type mice
- mice exhibit less time exploring the open arms of an elevated plus maze compared with wild-type mice

increased grooming behavior
- resulting in skin lesions

social withdrawal
- mice fail to spend more time with a novel social partner unlike wild-type mice
- mice prefer to interact with an empty cage rather than a social partner unlike wild-type mice
- mice spend less time interacting with a social partner than wild-type mice
- social withdrawal is not alleviated by cross fostering pups with wild-type dams

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

mammalian phenotype

behavior/neurological phenotype
- Normal - mice exhibit normal learning and memory in a Morris water maze

nervous system phenotype

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
- spine density is reduced compared to in wild-type mice
- the neck width of medium spiny neuron spines is slightly larger than in wild-type mice

abnormal miniature excitatory postsynaptic currents
- Normal - however, miniature excitatory postsynaptic current frequency and amplitude in the hippocampal CA1 sub-region are normal
- reduced frequency and peak amplitude in medium spiny neurons

abnormal postsynaptic density morphology
- mice exhibit abnormal post-synaptic density composition compared to in wild-type mice

abnormal striatum morphology
- mice exhibit striatal hypertrophy compared with wild-type mice

environmentally induced seizures
- Normal - however, no spontaneous seizures are observed
- mice occasionally exhibit handling-induced seizures unlike wild-type mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Shank3^tm2Gfng/Shank3^tm2Gfng
B6.129-Shank3/J

behavior/neurological phenotype

abnormal learning/memory/conditioning
- mice are incapable of completing pre-training tasks for the touchscreen pairwise discrimination test, showing a trend towards completing fewer trials in stage 1, significantly fewer trials is stage 2, and require more days to reach criterion in stage 3

hypoactivity
- mice show reduced activity in the open field

Genotype: Shank3^tm2Gfng/Shank3⁺
B6.129-Shank3/J

behavior/neurological phenotype

impaired discrimination learning
- Normal - however, mice exhibit normal open field activity and sociability in the three chamber test
- in the touchscreen pairwise discrimination task, mice are slower to reach criterion and exhibit trends toward making more errors (first trial errors) and more correction errors than wild-type mice

References

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):437-42PubMed: 21423165 MGI: J:171113

Additional References

Fourie C; Vyas Y; Lee K; Jung Y; Garner CC; Montgomery JM. 2018. Dietary Zinc Supplementation Prevents Autism Related Behaviors and Striatal Synaptic Dysfunction in Shank3 Exon 13-16 Mutant Mice. Front Cell Neurosci 12:374PubMed: 30405356 MGI: J:276078
Peixoto RT; Chantranupong L; Hakim R; Levasseur J; Wang W; Merchant T; Gorman K; Budnik B; Sabatini BL. 2019. Abnormal Striatal Development Underlies the Early Onset of Behavioral Deficits in Shank3B(-/-) Mice. Cell Rep 29(7):2016-2027.e4PubMed: 31722214 MGI: J:284647
Rhine MA; Parrott JM; Schultz MN; Kazdoba TM; Crawley JN. 2019. Hypothesis-driven investigations of diverse pharmacological targets in two mouse models of autism. Autism Res 12(3):401-421PubMed: 30653853 MGI: J:286911

Additional - Shank3^tm2Gfng related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Shank3-Alternate 2
- Probe:Shank3 Probe
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

Mutant 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.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x C57BL/6J (000664)
- C57BL/6J (000664) x Heterozygote
Citation
When using the Shank3B^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017688 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Shank3<tm2Gfng>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

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Licensing Information

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Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Also Known As:Shank3B-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Shank3tm2Gfng

Allele Symbol: Shank3tm2Gfng

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Shank3tm2Gfng/Shank3tm2Gfnginvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

integument phenotype

mammalian phenotype

nervous system phenotype

Genotype: Shank3tm2Gfng/Shank3tm2GfngB6.129-Shank3/J

behavior/neurological phenotype

Genotype: Shank3tm2Gfng/Shank3+B6.129-Shank3/J

behavior/neurological phenotype

References

Additional References

Additional - Shank3tm2Gfng related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

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:Shank3B^-

Shank3^tm2Gfng

Allele Symbol: Shank3^tm2Gfng

Genotype: Shank3^tm2Gfng/Shank3^tm2Gfng
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Genotype: Shank3^tm2Gfng/Shank3^tm2Gfng
B6.129-Shank3/J

Genotype: Shank3^tm2Gfng/Shank3⁺
B6.129-Shank3/J

Additional - Shank3^tm2Gfng related