B6.FVB-Tg(Shank3-EGFP)1Hzo/J

Stock number: 024033
Research areas: Neurobiology Research, Research Tools

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Tg(Shank3-EGFP)1Hzo
Name: transgene insertion 1, Huda Y Zoghbi
MGI accession ID: MGI:5515936
Generation method: Transgenic
Attributes: Reporter; Inserted expressed sequence
Marker symbol: Tg(Shank3-EGFP)1Hzo
Marker name: transgene insertion 1, Huda Y Zoghbi
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: Shank3,SH3 and multiple ankyrin repeat domains 3,mouse, laboratory; GFP,Green Fluorescent Protein,
Site of expression: EGFP is expressed and and Shank3 is overexpressed in dendritic spines in the cortex, hippocampus and striatum.
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.