SJL.129-Cd44^tm1Ugu/J

Stock number: 008008
Product name: CD44v7 KO
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These floxed mutant mice possess loxP sites flanking exon 6 of the Cd44 gene. This strain may be useful for generating conditional mutations in studies of multiple sclerosis (MS) and inflammatory diseases.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mice possess loxP sites on either side of exon 6 of the targeted gene. RT-PCR analysis reveals that exon 7 is not expressed in the floxed mice, and Southern blots confirm that 1.6kb of exon 7 was deleted during homologous recombination. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exon 6 and exon 7 deleted in the cre-expressing tissue(s). According to the donating investigator, homozygotes exhibit reduced incidence and severity of induced experimental autoimmune encephalomyelitis (EAE) when compared to wildtype controls. This mutant mouse strain may be useful in studies of multiple sclerosis (MS) and inflammatory diseases.

NOTE: Stock No. 008008 mice are on a unique "SJL/R" genetic background; the "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction.

NOTE: On a 129/Sv genetic background, homozygotes are resistant to trinitrobenzene sulfonic acid (TNBS)-induced colitis.

Development

A targeting vector containing a loxP site-flanked neomycin resistance cassette inserted upstream and a third loxP site inserted downstream of exon 6 of the targeted gene was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Approximately 1.6kb of exon 7 also was deleted from the targeted gene during homologous recombination. The resulting chimeric mice were bred to "SJL/R" mice (from Erasmus Medical Center, Rotterdam, The Netherlands) for 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, female and male mutant mice were bred together to preserve the unique genetic background of this strain.

NOTE: The "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction. A 27 SNP (single nucleotide polymorphism) panel analysis performed on the Cd44-mutant mice that were rederived by The Jackson Laboratory revealed 4 loci that were homozygous for markers other than SJL/J. These loci are on chromosome 3 (approximately 16.3 cM), chromosome 9 (approximately 6.6 cM), chromosome 11 (approximately 9.8 cM), and chromosome 18 (approximately 26.2 cM). The Jackson Laboratory obtained "SJL/R" splenocyte DNA from the Erasmus Medical Center and report an identical SNP profile using the same 27 SNP panel analysis.

Allele

Symbol: Cd44^tm1Ugu
Name: targeted mutation 1, Ursula Gunthert
MGI accession ID: MGI:2679704
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd44
Marker name: CD44 antigen
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A loxP site was inserted 3' of exon v6 while a neomycin resistance cassette with a 5' loxP site was inserted 5' of exon v6. During insertion, 1.6 kb of sequence was lost in the exon v7 region leading to deficient expression of this variant in homozygous mutant mice.