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Type Congenic; Mutant Strain; Targeted Mutation; Mating System Heterozygote x Heterozygote (Female x Male) Species laboratory mouse Generation N5+ (16-JAN-08) Donating Investigator 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 | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Congenic Nomenclature
Related Disease (OMIM) Terms
Williams-Beuren Syndrome; WBS Mammalian Phenotype Terms 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 (MGI Ref ID J:78711)
- adult female weight is 9% lower than in wild-type
- postnatal growth retardation (MGI Ref ID J:78711)
- mild growth retardation during the first weeks of postnatal development that persists in adult females
- nervous system phenotype
- decreased corpus callosum size (MGI Ref ID J:78711)
- average corpus callosum volume is smaller, however ventricle volumes are normal
- impaired synaptic plasticity (MGI Ref ID J:78711)
- synaptic plasticity in the hippocampal CA1 region is lower
- behavior/neurological phenotype
- abnormal contextual conditioning (MGI Ref ID J:78711)
- 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 (MGI Ref ID J:78711)
- remain on an accelerating rotarod for significantly shorter periods
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 | ||
| Common Name(s) | CLIP-L; | ||
| Mutation Made By | 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. | ||
| Gene Symbol and Name | Clip2, CAP-GLY domain containing linker protein 2 | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | CLIP; CLIP-115; CYLN2; Cyln2; KIAA0291; MGC11333; WBSCR3; WBSCR4; WSCR3; WSCR4; cytoplasmic linker 2; | ||
| 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] | ||
Genotyping Protocols
Clip2tm1.1Gal, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as homozygotes. Diet Information LabDiet® 5K52/5K67
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Clip2tm1.1Gal $291.90 Female or Male Homozygous for Clip2tm1.1Gal *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $472.80 Heterozygous for Clip2tm1.1Gal x Heterozygous for Clip2tm1.1Gal
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Clip2tm1.1Gal $379.50 Female or Male Homozygous for Clip2tm1.1Gal *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $614.70 Heterozygous for Clip2tm1.1Gal x Heterozygous for Clip2tm1.1Gal
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
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