These Shank3(+/ΔC) mice may be useful for studying behavioral and synaptic abnormalities associated with autism spectrum disorder.
Paul Worley, Johns Hopkins University School of Medic
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Hypomorph) | Shank3 | SH3 and multiple ankyrin repeat domains 3 |
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.
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.
Allele Name | targeted mutation 1.1, Paul Worley |
---|---|
Allele Type | Targeted (Hypomorph) |
Allele Synonym(s) | Shank3(deltaC); Shank3tm1.1Bxia |
Gene Symbol and Name | Shank3, SH3 and multiple ankyrin repeat domains 3 |
Gene Synonym(s) | |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 15 |
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. No wild-type protein is detected in homozygous mice but a lower molecular weight mutant protein is detected by western blot analysis. |
Mutations Made By | Bo Xiao, Johns Hopkins University School of Medic |
When 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.
When using the Shank3ΔC (Shank3Δ ex21) mouse strain in a publication, please cite the originating article(s) and include JAX stock #018398 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Shank3<tm1.1Pfw> |
Frozen Mouse Embryo | STOCK Shank3<tm1.1Pfw>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Shank3<tm1.1Pfw>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Shank3<tm1.1Pfw>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Shank3<tm1.1Pfw>/J Frozen Embryo | $3373.50 |
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 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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.