B6.129S7-Shank3^tm1Yhj/J

Stock number: 017442
Product name: Shank3^e4-9
Research areas: Neurobiology Research

Description

Shank3^e4-9 has a neo cassette replacing the ankyrin repeat domains (exons 4-9) of the Shank3 gene. Homozygous mice display abnormal social behaviors, communication patterns, repetitive behaviors, learning and memory. These mice may be useful for studying behavioral abnormalities associated with autism spectrum disorder.

Detailed description

In this strain, a neo cassette replaces exons 4-9 of SH3/ankyrin domain 3 (Shank3) gene. SHANK3 is a synaptic scaffolding protein, expressed in the postsynaptic density (PSD) of excitatory synapses, which contains five intragenic promoters 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 these Shank3^e4-9 mice, the neo cassette is inserted downstream of Promoter 2, making these mice deficient in Shank3a-b which are transcripts from Promoters 1-2. They do produce transcripts Shank3c-e from downstream Promoters 3-5. These mice display abnormal social behaviors, communication patterns, repetitive behaviors, learning and memory. Male mice also display severe motor coordination impairments. Shank3^e4-9 mice also exhibit morphological alterations in dendritic spines and are deficient in long-term potentiation. 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 4-9 of SH3/ankyrin domain 3 (Shank3) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2-derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were backcrossed for at least 7 generations to C57BL/6J background. The donating investigator states that the naturally occurring Disc1 (Disrupted in Schizophrenia 1) mutation in the 129SvEv ES cells was bred out of this Shank3^e4-9 line. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation.

Allele

Symbol: Shank3^tm1Yhj
Name: targeted mutation 1, Yong-hui Jiang
MGI accession ID: MGI:5056336
Generation method: Targeted
Marker symbol: Shank3
Marker name: SH3 and multiple ankyrin repeat domains 3
Chromosome: 15
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: Exons 4 through 9, which encode the ankyrin repeats, were replaced with a neo cassette. The absence of the 190 kDa but presence of of the 170 kDa and 140 kDa peptides was confirmed by western blot analysis on brian extracts. The a and b isoforms are deleted.