Overview

Also Known As:CLIP-L

These knockout mice exhibit impaired motor coordination. Homozygotes exhibit a mild growth retardation with female adult homozygotes having a lower body weight and smaller body length.

Donating Investigator

Dr. Niels Galjart, Erasmus Medical Centre

Genetic overview

Genetic Background	Generation

Clip2^tm1.1Gal

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Clip2	CAP-GLY domain containing linker protein 2

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable and fertile. Female homozygotes adults have lower body weights and smaller body length when compared to wildtype. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of brain tissue. A splice acceptor site introduced into the lacZ reporter cassette results in a hybrid Clip2-lacZ transcript. Beta galactosidase staining is observed primarily in the hippocampus and in other areas of the brain. Homozygotes exhibit a mild growth retardation. The average copus callosum volume is significantly smaller than wildtype. Homozygotes and heterozygotes exhibit abnormal behavior indicative of hippocampal defects. In contextual fear-conditioning tests, mutant mice have a diminished response, although in cued fear-conditioning tests mutant mice exhibit normal behavior. Synaptic plasticity in the CA1 area of the hippocampus is decreased in mutant mice. Both heterozygotes and homozygotes exhibit impaired motor coordination. Abnormal protein distribution on microtubules, with increased dynactin and CLIP-170 at the distal ends, is found in fibroblasts from embryonic and adult homozygotes. This mutant mouse strain may be useful in studies of neurodevelopment and Williams-Beuren syndrome.

Development

A targeting vector containing a loxP flanked puromycin gene, a lacZ gene and polyadenylation site sequence was inserted downstream of the endogenous locus. This construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were then electroporated with a second targeting vector containing loxP flanked neomycin resistance and herpes simplex virus thymidine kinase genes, which was inserted into intron 2. Correctly targeted ES cells carrying both constructs targeted to the same allele were electroporated with a construct containing a cre gene under the control of the thymidine kinase promoter and hygromycin resistance gene to remove the selection cassettes and most of the encoding sequence (exons 3 through 17). Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to female C57BL/6 mice, and then backcrossed to C57BL/6NHsd for 7 generations and to C57BL/6J for 3 generations prior to arriving at The Jackson Laboratory.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Beta galactosidase staining is observed primarily in the hippocampus and in other areas of the brain.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Hoogenraad CC; Koekkoek B; Akhmanova A; Krugers H; Dortland B; Miedema M; van Alphen A; Kistler WM; Jaegle M; Koutsourakis M; Van Camp N; Verhoye M; van der Linden A; Kaverina I; Grosveld F; De Zeeuw CI; Galjart N. 2002. Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat Genet 32(1):116-27PubMed: 12195424 MGI: J:78711

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Genetics

Clip2^tm1.1Gal

Allele Symbol: Clip2^tm1.1Gal

Allele Name	targeted mutation 1.1, Niels Galjart
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	CLIP-L
Gene Symbol and Name	Clip2, CAP-GLY domain containing linker protein 2
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Beta galactosidase staining is observed primarily in the hippocampus and in other areas of the brain.
Strain of Origin	129P2/OlaHsd
Chromosome	5
Molecular Note	ES cells containing Cyln2^tm1Gal were electroporated with a construct containing cre recombinase and a hygromycin resistance gene. Expression of cre resulted in the excision of the floxed region containing both previously inserted selection genes and exons 3 through 17. Neither normal transcript nor normal protein was detected in homozygous mutant mice by Northern and Western blot analyses. Recombination left the previously inserted lacZ gene in frame with the endogenous promoter, which drove its expression.
Mutations Made By	Dr. Niels Galjart, Erasmus Medical Centre

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Williams-Beuren syndrome

Research Areas By Phenotype

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

Neurobiology Research
- Behavioral and Learning Defects
- Neurodevelopmental Defects
- Epilepsy
- lacZ expression in neural tissue

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Clip2^tm1.1Gal/Clip2⁺
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

abnormal contextual conditioning behavior
- in a contextual fear-conditioning test, show a smaller increase in average freezing time after foot shock than in wild-type, however no differences are seen in a cued fear-conditioning test or elevated zero-maze test, indicating hippocampal defects

impaired coordination
- remain on an accelerating rotarod for significantly shorter periods

growth/size/body region phenotype

decreased body weight
- adult female weight is 9% lower than in wild-type

postnatal growth retardation
- mild growth retardation during the first weeks of postnatal development that persists in adult females

nervous system phenotype

decreased corpus callosum size
- average corpus callosum volume is smaller, however ventricle volumes are normal

impaired synaptic plasticity
- synaptic plasticity in the hippocampal CA1 region is lower

References

Hoogenraad CC; Koekkoek B; Akhmanova A; Krugers H; Dortland B; Miedema M; van Alphen A; Kistler WM; Jaegle M; Koutsourakis M; Van Camp N; Verhoye M; van der Linden A; Kaverina I; Grosveld F; De Zeeuw CI; Galjart N. 2002. Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat Genet 32(1):116-27PubMed: 12195424 MGI: J:78711

Additional - Clip2^tm1.1Gal related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Clip2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the CLIP-L mouse strain in a publication, please cite the originating article(s) and include JAX stock #007566 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Clip2<tm1.1Gal>

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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:CLIP-L

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Clip2tm1.1Gal

Allele Symbol: Clip2tm1.1Gal

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Clip2tm1.1Gal/Clip2+involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

nervous system phenotype

References

Additional - Clip2tm1.1Gal related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

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

Clip2^tm1.1Gal

Allele Symbol: Clip2^tm1.1Gal

Genotype: Clip2^tm1.1Gal/Clip2⁺
involves: 129P2/OlaHsd * C57BL/6

Additional - Clip2^tm1.1Gal related