B6;129P2-Clstn2^tm1Amcr/J

Stock number: 032651
Product name: Clstn2 knock-out , Clstn2^-/- , Clstn2-KO
Research areas: Neurobiology Research, Research Tools

Description

Clstn2 knock-out mice (Clstn2^-/- , Clstn2-KO) may exhibit reduced GABAergic interneurons, behavioral changes (hyperactivity), hippocampus-dependent spatial learning/memory deficiencies, stereotyped behavior and sex-specific social and emotional abnormalities. These characteristics may be genetic background dependent (see detailed description). Clstn2 knock-out mice may be useful for neurological studies of cognitive function and brain development, specifically in development of inhibitory synapses and parvalbumin interneurons, as well as neuropsychiatric disorders or characteristics of autism spectrum disorder.

Detailed description

Calsyntenins in the brain function to regulate balance between excitatory and inhibitory neuronal functions. The Clstn2 gene encodes calsyntenin-2, a neuronal cell surface synaptic protein known to function in learning and memory. Human mutations in CLSTN2 have been identified in patients with autism spectrum disorder.

Clstn2^-/- (Clstn2-KO) mice available from The Jackson Laboratory (Stock No. 032651) were backcrossed two generations onto C57BL/6J prior to arrival in October 2018. The donating investigator reports the phenotype of the mice (N2 onto C57BL/6J) was not specifically characterized, and could vary from that originally described below. We may modify our strain description if necessary as published results become available.

Mice homozygous for the Clstn2 knock-out allele (Clstn2^-/- or Clstn2-KO) may have reduced GABAergic interneurons, behavioral changes (hyperactivity), hippocampus-dependent spatial learning/memory deficiencies, stereotyped behavior and sex-specific social and emotional abnormalities. These characteristics may be genetic background dependent.

Specifically, Clstn2^-/- mice backcrossed nine generations onto C57BL/6J exhibit reductions in parvalbumin-positive interneuron density (cortex and hippocampal CA1/CA3 areas), inhibitory synaptic markers and hippocampal functional inhibitory synapses. [Lipina et al. 2016 Neuropsychopharmacology 41:802]

For Clstn2-KO mice on a mixed C57BL/6NCrl;C57BL/6J genetic background, the homozygous males (but not females) show deficient social motivation and social recognition without any changes in olfactory function, as well as greater emotionality in response to highly aversive conditions. [Ranneva et al. 2017 Behav Brain Res 332:343]

Development

The Clstn2 knock-out allele (Clstn2^-) was donated by Dr. Ann Marie Craig (University of British Columbia) and generated as described in Lipina et al. 2016 Neuropsychopharmacology 41:802 [PMID:26171716].

A targeting vector with a loxP::frt-neo-frt cassette was designed to replace exon 3 of the calsyntenin 2 locus (Clstn2) on chromosome 9. The donating investigator reports that this construct was electroporated into 129P2/OlaHsd-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric animals were bred with C57BL/6J mice for germline transmission of the Clstn2^- allele. The Clstn2^- colony was backcrossed to C57BL/6J inbred mice for two generations by the donating laboratory prior to sending homozygous (Clstn2^-/-) males to The Jackson Laboratory in 2010 (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm may be used to fertilize C57BL/6J oocytes (Stock No. 000664).



In 2021, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the mice sent to The Jackson Laboratory Repository. Two of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Clstn2^tm1Amcr
Name: targeted mutation 1, Ann Marie Craig
MGI accession ID: MGI:6093445
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Clstn2
Marker name: calsyntenin 2
Marker synonyms: 2900042C18Rik; alcagamma; ALC-GAMMA; CDHR13; CS2; Cst-2; CSTN2
Chromosome: 9
Strain of origin: 129P2/OlaHsd
Molecular note: A BAC clone from the 129/S7 bMQ library was used to construct a targeting vector by replacing exon 3 with a loxP site and an FRT site flanked neomycin resistance gene cassette. Western blots confirmed the loss of expression from this null allele.