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.
Guoping Feng, Massachusetts Institute of Technology
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.
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.
|Allele Name||targeted mutation 2, Guoping Feng|
|Gene Symbol and Name||Shank3, SH3/ankyrin domain gene 3|
|Gene Synonym(s)||AI841104; DEL22q13.3; PROSAP2; PSAP2; ProSAP2; Prosap2; SCZD15; SPANK-2; expressed sequence AI841104|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|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.|
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.
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