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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N5F1pN1
Generation DefinitionsDonating Investigator Dr. Niels Galjart, Erasmus Medical Centre 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.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of lacZ
View Strains carrying other alleles of lacZ (267 strains)
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms provided by MGI
- 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; WBS
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Clip2tm1.1Gal/Clip2+
involves: 129P2/OlaHsd * C57BL/6
- growth/size phenotype
- decreased body weight
- adult female weight is 9% lower than in wild-type (MGI Ref ID J:78711)
- postnatal growth retardation
- mild growth retardation during the first weeks of postnatal development that persists in adult females (MGI Ref ID J:78711)
- nervous system phenotype
- decreased corpus callosum size
- average corpus callosum volume is smaller, however ventricle volumes are normal (MGI Ref ID J:78711)
- impaired synaptic plasticity
- synaptic plasticity in the hippocampal CA1 region is lower (MGI Ref ID J:78711)
- 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 (MGI Ref ID J:78711)
- impaired coordination
- remain on an accelerating rotarod for significantly shorter periods (MGI Ref ID J:78711)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Neurobiology Research
lacZ expression in neural tissue
Behavioral and Learning Defects
Epilepsy
Neurodevelopmental Defects
| Allele Symbol | Clip2tm1.1Gal | ||
|---|---|---|---|
| Allele Name | targeted mutation 1.1, Niels Galjart | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | CLIP-L; | ||
| Mutation Made By | Dr. Niels Galjart, Erasmus Medical Centre | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Site of Expression | Beta galactosidase staining is observed primarily in the hippocampus and in other areas of the brain. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | ES cells containing Cyln2tm1Gal 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. [MGI Ref ID J:78711] | ||
| Gene Symbol and Name | Clip2, CAP-GLY domain containing linker protein 2 | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | CLIP; CLIP-115; CYLN2; Cyln2; WBSCR3; WBSCR4; WSCR3; WSCR4; cytoplasmic linker 2; | ||
Genotyping Protocols
Clip2tm1.1Gal, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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):116-27. [PubMed: 12195424] [MGI Ref ID J:78711]
Clip2tm1.1Gal relatedSchmidt N; Basu S; Sladecek S; Gatti S; van Haren J; Treves S; Pielage J; Galjart N; Brenner HR. 2012. Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane. J Cell Biol 198(3):421-37. [PubMed: 22851317] [MGI Ref ID J:191317]
Stepanova T; Smal I; van Haren J; Akinci U; Liu Z; Miedema M; Limpens R; van Ham M; van der Reijden M; Poot R; Grosveld F; Mommaas M; Meijering E; Galjart N. 2010. History-dependent catastrophes regulate axonal microtubule behavior. Curr Biol 20(11):1023-8. [PubMed: 20471267] [MGI Ref ID J:161962]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as homozygotes.
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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