STOCK Cdh11^tm1Mta/HensJ

Stock number: 023494
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

This Cdh11 knockout strain produces a non-functional truncated protein and is useful in studies of bone development, limbic system synaptic connections and inflammation.

Detailed description

The protein encoded by the Cdh11, cadherin 11, gene is involved in calcium-dependent cell-cell adhesion, with roles in bone development and inflammation. Mice that are homozygous for the targeted mutation are viable and fertile, but develop susceptibility to seizures when older (onset age). Western blot analysis of E10.5 homozygous embryos revealed expression of a 97kDa protein due to cryptic splicing. The truncated protein is not functional. Homozygotes exhibit reduced frontal suture calcified area and reduced bone density of the femoral metaphyses and calvaria diploe. Long-term potentiation in CA1 region of hippocampus is enhanced and saturation increased in mutant mice, which also exhibit reduced fear/anxiety response behaviors. Homozygotes are resistant to inflammatory arthritis, have hypoplastic synovial lining and a disorganized synovial reaction to inflammation. In response to bleomycin induced pulmonary fibrosis, mutant mice exhibit decreased fibrotic endpoints with reduced TGF-beta levels in bronchoalveolar lavage and primary alveolar macrophages, when compared to wildtype controls. Older homozygotes, 1 year or more in age, mice suffer from seizures.

Development

A targeting vector designed by Dr. Masatoshi Takeichia (Kyoto University, Japan) containing a PGK-NEO cassette was used to disrupt most of exon 16, which encodes the last 56 amino acids of the extracellular domain and most of the transmembrane domain. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then crossed to CD-1 mice by Dr. Julie Hens. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Cdh11^tm1Mta
Name: targeted mutation 1, Masatoshi Takeichi
MGI accession ID: MGI:1861184
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cdh11
Marker name: cadherin 11
Chromosome: 8
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: Most of exon 16, encoding the last 56 amino acids of the extracellular domain and most of the transmembrane domain, was replaced with a neomycin cassette. A 97 kD truncated protein is expressed from this allele; authors state that this is a non-functional protein, and furthermore does not have any dominant negative effects.