These Cd86 knock-out mice develop spontaneous autoimmune peripheral polyneuropathy marked by limb paralysis.
Dr. Jeffrey A. Bluestone, University of California, San Francisco
The NOD.129S4-Cd86tm1Shr/JbsJ homozygous mice fail to produce functional protein in T cells. Mice carrying this allele are protected from diabetes. Some homozygote mice have delayed onset peri-insulitis, which does not progress to severe insulitis. Beginning at 20 weeks of age, homozygous mice begin developing spontaneous autoimmune peripheral polyneuropathy marked by symmetrical mild hind limb paralysis. By 32 weeks of age 100% female and 30% males are severely affected with hind limb paralysis and moderate foreleg paralysis. Histological evaluation shows severe inflammation and mononuclear infiltrates in the peripheral nervous system. Skeletal muscle of severely affected mice showed focal neurogenic atrophy, but no cellular infitration. No detectable lesions were found in the brain or spinal cord. This phenotype has not been observed on C57BL/6 or 129 backgrounds (Salomon et al, 2001). NOD.129S4- Cd86tm1Shr /JbsJ provides a useful model for studying spontaneous autoimmune neuritis that can give us new insights into complex autoimmune diseases.
A targeting vector containing a neomycin cassette under the control of the mouse phosphoglycerol kinase (PGK) promoter was used to disrupt the exon within the Cd86 gene, encoding the Ig-V-like domain of the protein in J1 (129S4) embryonic stem (ES) cells. ES cells were injected into C57BL/6 blastocysts. To establish a colony and germ line transmission chimeric mice were backcrossed to 129S4, prior to intercrossing to generate mice homozygous for this allele (Borriello et al, 1997). Salomon et al, 2001 backcrossed to NOD for 9 generations prior to 15 generations of intercrossing. In 2003, NOD.129S4- Cd86tm1Shr /Jbs arrived at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Arlene H Sharpe|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||B7-2-; B7.2 KO|
|Gene Symbol and Name||Cd86, CD86 antigen|
|Gene Synonym(s)||B7-2; B7.2; B70; CD28 antigen ligand; CD28LG2; Cd28l2; Cd28l2; LAB72; Ly-58; Ly-58; Ly58; Ly58; MB7-2; lymphocyte antigen 58|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin selection cassette replaced an exon encoding the IgV-like domain of the protein and flanking genomic sequences. FACS analysis on splenocytes and LPS-stimulated B cells derived from homozygous mice confirmed that no functional protein was encoded by this allele.|
|Mutations Made By|| |
Arlene Sharpe, Harvard Medical School
When held in a live colony, this strain may maintained homozygote x homozygote. Homozygotes are viable and fertile. Breeder replacement at 5-6 months of age will reduce potential complications attributed to limb paralysis. Mice exhibiting hind limb weakness should be euthanized as they will succumb to the disease.
When using the NOD.129S4-Cd86tm1Shr/JbsJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #004762 in your Materials and Methods section.
|Heterozygous for Cd86<tm1Shr>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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