Overview

Also Known As:Caspr2-

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, Cntnap2^tlacz/tlacz mice (Stock No. 028635) contain a tau-LacZ gene creating a knock-in/knock-out Cntnap2 allele.

Donating Investigator

Elior Peles, Weizmann Institute of Science

Genetic overview

Genetic Background	Generation
	N11+pN2F8 (2020-08-07 00:00:00)

Cntnap2^tm1Pele

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cntnap2	contactin associated protein-like 2

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Research Applications

Mouse/Human Gene Homologs
Neurobiology Research
Research Tools
Developmental Biology Research

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Base Price

Starting at:

$236.78 Domestic price for female 4-week

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Details

Detailed Description

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.

Development

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.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Poliak S; Salomon D; Elhanany H; Sabanay H; Kiernan B; Pevny L; Stewart CL; Xu X; Chiu SY; Shrager P; Furley AJ; Peles E. 2003. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162(6):1149-60PubMed: 12963709 MGI: J:85502

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Genetics

Cntnap2^tm1Pele

Allele Symbol: Cntnap2^tm1Pele

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

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

cortical dysplasia-focal epilepsy syndrome

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

autism spectrum disorder

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
- Epilepsy
Neurobiology Research
- Behavioral and Learning Defects
  - high anxiety
- Epilepsy
- Neurodevelopmental Defects
  - Autism
Research Tools
- Neurobiology Research
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Cntnap2^tm1Pele/Cntnap2^tm1Pele
B6.129-Cntnap2

behavior/neurological phenotype

abnormal inhibitory learning
- mutants perform similarly to wild-type mice in the Morris water maze probe trials, however in a classic reversal task using the Morris water maze, mutants show impaired learning of the new location of the platform and perform poorly in the probe test

abnormal motor coordination/balance
- mutants perform better than wild-type mice on the rotorod

abnormal nest building behavior
- mutants are impaired in nest-building behavior, scoring less than half of the wild-type criterion
- mutants treated with the drug Risperidone exhibit rescue of the nesting deficits

decreased thermal nociceptive threshold
- Normal - however, no differences seen in the acoustic startle response or prepulse inhibition
- mutants exhibit hyperreactivity to thermal sensory stimuli

decreased vocalization
- mutants emit a lower number of ultrasonic calls than wild-type mice at all ages

environmentally induced seizures
- seizures are induced by mild stressors during routine handling

hyperactivity
- mutants show greater locomotor activity than wild-type mice in the open field test
- mutants treated with the drug Risperidone exhibit rescue of the hyperactivity

increased grooming behavior
- mutants spend almost 3 times more time grooming than wild-type mice

increased stereotypic behavior
- in the spontaneous alternation T maze test, mutants show higher number of no alternations in a standard 10 trial test, indicating preservation
- mutants treated with the drug Risperidone exhibit rescue of the repetitive behavior/perseveration

seizures
- mutants older than 6 months of age commonly exhibit spontaneous seizures

social withdrawal
- in a juvenile play test, mutants at P21 spend less time interacting with each other and instead show increased repetitive behaviors such as grooming and digging
- in a three-chamber social interaction test in adults, mutants do not show a preference for the cup with a mouse as seen in wild-type mice

cellular phenotype

abnormal neuronal migration
- ectopic neurons are seen in the corpus callosum of mutants at P14
- mutants exhibit abnormal migration of cortical projection neurons as evidenced by the higher numbers of CUX1+ cells in deep cortical layers

integument phenotype

decreased thermal nociceptive threshold
- Normal - however, no differences seen in the acoustic startle response or prepulse inhibition
- mutants exhibit hyperreactivity to thermal sensory stimuli

mammalian phenotype

behavior/neurological phenotype
- Normal - mutants treated with the drug Risperidone exhibit rescue of the hyperactivity, repetitive behavior/perseveration and nesting deficits
- Normal - no differences are seen in the light-dark exploration test between mutants and wild-type mice

nervous system phenotype

abnormal brain interneuron morphology
- mutants exhibit a decrease in the number of GABAergic interneurons in all laminae and in the striatum
- mutants exhibit a reduction in parvalbumin+ interneurons in the hippocampus

abnormal brain wave pattern
- at 8 months of age, freely moving mutants exhibit generalized interictal spike discharges during slow-wave sleep

abnormal corpus callosum morphology
- ectopic neurons are seen in the corpus callosum of mutants at P14; ectopic neurons are seen through adulthood

abnormal neuron physiology
- however, neither the average firing amplitude nor the average firing rate are changed, suggesting that the defect is due to a network dysfunction rather than abnormalities in neuronal activity or conduction per se
- mutants exhibit reduced cortical neuronal synchrony as indicated by two-photon calcium imaging of layer II/III neurons from somatosensory cortex showing that neuronal firing pattern is highly asynchronous compared to wild-type mice

abnormal neuronal migration
- ectopic neurons are seen in the corpus callosum of mutants at P14
- mutants exhibit abnormal migration of cortical projection neurons as evidenced by the higher numbers of CUX1+ cells in deep cortical layers

astrocytosis
- Normal - however, neuronal loss is not seen in the hippocampus
- reactive astrocytosis is seen throughout the hippocampus after onset of seizures, especially in the hilus

environmentally induced seizures
- seizures are induced by mild stressors during routine handling

seizures
- mutants older than 6 months of age commonly exhibit spontaneous seizures

taste/olfaction phenotype

abnormal olfaction
- mutants perform better than wild-type mice in the buried food test, indicating better olfaction

References

Poliak S; Salomon D; Elhanany H; Sabanay H; Kiernan B; Pevny L; Stewart CL; Xu X; Chiu SY; Shrager P; Furley AJ; Peles E. 2003. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162(6):1149-60PubMed: 12963709 MGI: J:85502

Additional References

Reed MD; Yim YS; Wimmer RD; Kim H; Ryu C; Welch GM; Andina M; King HO; Waisman A; Halassa MM; Huh JR; Choi GB. 2020. IL-17a promotes sociability in mouse models of neurodevelopmental disorders. Nature 577(7789):249-253PubMed: 31853066 MGI: J:289937

Additional - Cntnap2^tm1Pele related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Cntnap2alternate2
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

AX12 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Cntnap2<tm1Pele>

Related Products and Services

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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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:Caspr2-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Cntnap2tm1Pele

Allele Symbol: Cntnap2tm1Pele

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Cntnap2tm1Pele/Cntnap2tm1PeleB6.129-Cntnap2

behavior/neurological phenotype

cellular phenotype

integument phenotype

mammalian phenotype

nervous system phenotype

taste/olfaction phenotype

References

Additional References

Additional - Cntnap2tm1Pele related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Cntnap2^tm1Pele

Allele Symbol: Cntnap2^tm1Pele

Genotype: Cntnap2^tm1Pele/Cntnap2^tm1Pele
B6.129-Cntnap2

Additional - Cntnap2^tm1Pele related