NOD.129S4-Cd86^tm1Shr/JbsJ

Stock number: 004762
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

These Cd86 knock-out mice develop spontaneous autoimmune peripheral polyneuropathy marked by limb paralysis.

Detailed description

The NOD.129S4-Cd86^tm1Shr/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- Cd86^tm1Shr /JbsJ provides a useful model for studying spontaneous autoimmune neuritis that can give us new insights into complex autoimmune diseases.

Development

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- Cd86^tm1Shr /Jbs arrived at The Jackson Laboratory.

Allele

Symbol: Cd86^tm1Shr
Name: targeted mutation 1, Arlene H Sharpe
MGI accession ID: MGI:1861805
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: B7.2 KO; B7-2-
Marker symbol: Cd86
Marker name: CD86 antigen
Marker synonyms: B7.2; B70; B7-2; Cd28l2; CD28LG2; LAB72; Ly58; Ly-58; MB7-2
Chromosome: 16
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.