B6N.129S4-Shank2^tm1Mgle/CsbdJ

Stock number: 033667
Product name: Shank2^-
Research areas: Neurobiology Research

Description

Shank2^- mice have a loxP-flanked neo cassette replacing exons 6-7 of the SH3 and multiple ankyrin repeat domains 2 (Shank2) gene, abolishing endogenous gene function. These mice are useful when studying autism spectrum disorder (ASD).

Detailed description

The Shank2^- allele has a loxP-flanked neo cassette replacing exons 6-7 of the SH3 and multiple ankyrin repeat domains 2 (Shank2) gene, abolishing endogenous gene function. Shank2 encodes a multi-domain scaffolding protein and signaling adaptor enriched at excitatory neuronal synapses. Mutations in SHANK2 have been associated with the onset of autism spectrum disorder (ASD) characterized by impaired social interaction and communication, and restricted and repetitive behaviors. Exons 6 and 7 encode a large portion of the PDZ domain in both Shank2 splice variants (Shank2a and Shank2b). They exhibit ASD-like behaviors including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function.

Colonists at The Jackson Laboratory report increased aggression and dermatitis in homozygous mice. For this reason, this colony is maintained by breeding heterozygous mice to non-carrier (wildtype) mice from the colony, or to C57BL/6NJ inbred mice (Stock No. 005304).

Development

The Shank2^- targeting vector was designed to replace exons 6-7 of the SH3 and multiple ankyrin repeat domains 2 (Shank2) gene with a loxP-flanked neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6N blastocysts and the resulting chimeric males were bred to C57BL/6NHsd females. Offspring were backcrossed to C57BL/6NHsd mice for at least ten generations. Cryopreserved embryos were sent to The Jackson Laboratory Repository. Upon arrival, frozen embryos were used to rederive a live colony. Next, the colony was bred to C57BL/6NJ to ensure the Dock2^Hsd allele was removed and replaced with the C57BL/6NJ-derived Dock2 allele.

Allele

Symbol: Shank2^tm1Mgle
Name: targeted mutation 1, Min Goo Lee
MGI accession ID: MGI:5437479
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Shank2
Marker name: SH3 and multiple ankyrin repeat domains 2
Marker synonyms: AUTS17; CortBP1; CTTNBP1; ProSAP1; SHANK; Shank2E; SPANK-3
Chromosome: 7
Strain of origin: 129S4/SvJae
Molecular note: An approximately 3.1 kb genomic fragment including exons 6 and 7 was replaced with a floxed neo cassette via homologous recombination. Western blot analysis confirmed the absence of protein expression in the brains of homozygous mice.