Description

Strain Information

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 Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Clip2^tm1.1Gal/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

Genes & Alleles

Gene & Allele Information

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

Genotyping Information

Genotyping Protocols

Clip2^tm1.1Gal, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Health & husbandry

Health & Colony Maintenance Information

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

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Control Information

	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.

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

The Jackson Laboratory's Genotype Promise

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.

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