Cntnap2 knock-out mice mice exhibit hyperactivity, social and communication behavioral impairment, spontaneous seizures, abnormal cortical neuron migration, and abnormal neural synchrony. They may be useful in studies related to Cortical Dysplasia-Focal Epilepsy Syndrome and autism spectrum disorders.
Of note, Cntnap2tlacz/tlacz mice (Stock No. 028635) contain a tau-LacZ gene creating a knock-in/knock-out Cntnap2 allele.
Elior Peles, Weizmann Institute of Science
Genetic Background | Generation |
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N11+pN2F9
|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Cntnap2 | contactin associated protein-like 2 |
No gene product (mRNA or protein) is detected by RT-PCR, Western blot, or immunoprecipitation analysis of brain tissue from homozygous Cntnap2 (contactin associated protein-like 2) knockout animals. Homozygous mice older than 6 months of age exhibit handling-induced and spontaneous seizures.
Abnormal organization of neurons in the cortex and fewer parvalbumin-positive interneurons in the hippocampus are observed in homozygotes. Homozygotes exhibit an asynchronous neuronal firing pattern, but no defects in peripheral and central nerve conductance. Homozygotes also display hyperreactivity in open field tests and to thermal sensory stimuli. In buried food olfaction analysis, homozygotes perform better than wildtype controls. Fewer ultrasonic vocalizations are observed in homozygous pups. Mutant mice exhibit impaired social behavior: less interaction, increased grooming and digging, impaired nest building. Risperidone (atypical antipsychotic drug) treatment reduced the phenotype severity of mutant mice.
Contactin associated protein-like 2, a member of the neurexin superfamily, is critical for proper potassium ion channel localization in myelinated axons at the juxtaparanodal region. Mutations in human CNTNAP2 have been found to play a role in cortical dysplasia-focal epilepsy syndrome and autism spectrum disorders.
Mice that are homozygous for this targeted mutation are viable, fertile, and normal in size.
A targeting vector containing the neomycin resistance gene was used to disrupt exon 1. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were used to generate chimeric animals via aggregation. The resulting chimeric animals were crossed to ICR mice, and then crossed to 129/SvEv and C57BL/6J. The mice were then backcrossed to C57BL/6J for more than 10 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
Allele Name | targeted mutation 1, Elior Peles |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Caspr2- |
Gene Symbol and Name | Cntnap2, contactin associated protein-like 2 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 6 |
Molecular Note | Exon 1, which contains the start codon encodes the signal peptide, was replaced with a neomycin selection cassette inserted by homologous recombination. Transcript was undetected by RT-PCR analysis of homozygous mutant brain RNA. Protein was undetected in the central nervous system of homozygous mutant mice by immunoprecipitation and Western blot analysis. Similarly, no specific staining was observed by immunolabeling of sciatic nerve tissue. |
Mutations Made By | Elior Peles, Weizmann Institute of Science |
When maintaining a live colony, these mice can be bred as homozygotes. Homozygotes older than 6 months can have spontaneous seizures and seizures induced by mild stress, such as handling.
When using the Caspr2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017482 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Cntnap2<tm1Pele> |
Frozen Mouse Embryo | B6.129(Cg)-Cntnap2<tm1Pele>/J | $2595.00 |
Frozen Mouse Embryo | B6.129(Cg)-Cntnap2<tm1Pele>/J | $2595.00 |
Frozen Mouse Embryo | B6.129(Cg)-Cntnap2<tm1Pele>/J | $3373.50 |
Frozen Mouse Embryo | B6.129(Cg)-Cntnap2<tm1Pele>/J | $3373.50 |
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