Shank3 transgenic mice express EGFP and overexpress Shank3 in dendritic spines in the cortex, hippocampus and striatum. These mice may be useful for studying behavioral abnormalities associated with autism spectrum disorder (ASD) caused by SHANK3 duplications.
Huda Zoghbi, Baylor College of Medicine
Genetic Background | Generation |
---|---|
|
Allele Type |
---|
Transgenic (Reporter, Inserted expressed sequence) |
Shank3 transgenic mice overexpress a wild-type mouse Shank3 (SH3/ankyrin domain gene 3) gene and EGFP directed by Shank3 promoter/enhancer regions on the BAC transgene. 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. These Shank3 transgenic mice express 1.2-fold to twofold higher levels of each of the three major Shank3 isoforms (α, β and γ), with 50% more total Shank3 protein in dendritic spines in the cortex, hippocampus and striatum. Hemizygous mice are viable and fertile. They display a hyperkinetic phenotype that resembles mania. They exibit increased locomotor activity and speed in the open field test, and hyperactivity which was aggravated after injection of amphetamine. Shank3 transgenic mice also display a lower duration of immobility during the tail-suspension test, elevated acoustic startle response with reduced prepulse inhibition (PPI), abnormal circadian rhythms, decreased social interactions, seizures, and hyperphagia-like behavior. Transgenic mice responded well to the anticonvulsant drug valproate.
Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 75kb BAC (#RP23-278D8) containing the entire mouse Shank3 (SH3/ankyrin domain gene 3) gene. This BAC was modified to contain a Kozak sequence (ACCATGG) followed by enhanced green fluorescent protein (EGFP) sequence at the start codon of Shank3. The linearized construct was microinjected into fertilized FVB/N oocytes. Founder mice were bred to FVB/N mice and subsequently maintained by breeding transgenic mice with C57BL/6J inbred mice for at least 5 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | GFP, Green Fluorescent Protein, |
---|---|
Expressed Gene | Shank3, SH3 and multiple ankyrin repeat domains 3, mouse, laboratory |
Site of Expression | EGFP is expressed and and Shank3 is overexpressed in dendritic spines in the cortex, hippocampus and striatum. |
Allele Name | transgene insertion 1, Huda Y Zoghbi |
---|---|
Allele Type | Transgenic (Reporter, Inserted expressed sequence) |
Allele Synonym(s) | EGFP-Shank3; Shank3-EGFP |
Gene Symbol and Name | Tg(Shank3-EGFP)1Hzo, transgene insertion 1, Huda Y Zoghbi |
Gene Synonym(s) | |
Promoter | Shank3, SH3 and multiple ankyrin repeat domains 3, mouse, laboratory |
Expressed Gene | GFP, Green Fluorescent Protein, |
Expressed Gene | Shank3, SH3 and multiple ankyrin repeat domains 3, mouse, laboratory |
Site of Expression | EGFP is expressed and and Shank3 is overexpressed in dendritic spines in the cortex, hippocampus and striatum. |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | Bacterial artificial chromosome RP23-278D8 was modified to contain a Kozak sequence (ACCATGG) followed by enhanced green fluorescent protein (EGFP) sequence at the start codon. Line 1 was generated. Mice carrying this transgene overexpress all 3 of the major Shank3 isoforms. |
When maintaining a live colony hemizygous mice may be bred to wildtype (noncarrier) mice from the colony or to C57BL/6J (Stock No. 000664).
When using the B6.FVB-Tg(Shank3-EGFP)1Hzo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024033 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous or Non carrier for Tg(Shank3-EGFP)1Hzo |
Frozen Mouse Embryo | B6.FVB-Tg(Shank3-EGFP)1Hzo/J | $2595.00 |
Frozen Mouse Embryo | B6.FVB-Tg(Shank3-EGFP)1Hzo/J | $2595.00 |
Frozen Mouse Embryo | B6.FVB-Tg(Shank3-EGFP)1Hzo/J | $3373.50 |
Frozen Mouse Embryo | B6.FVB-Tg(Shank3-EGFP)1Hzo/J | $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.