B6.129P2-Clip2^tm1.1Gal/J

Stock number: 007566
Product name: CLIP-L
Research areas: Neurobiology Research

Description

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.

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.

Allele

Symbol: Clip2^tm1.1Gal
Name: targeted mutation 1.1, Niels Galjart
MGI accession ID: MGI:2387833
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Clip2
Marker name: CAP-GLY domain containing linker protein 2
Chromosome: 5
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: Beta galactosidase staining is observed primarily in the hippocampus and in other areas of the brain.
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.