BXSB.129S2(B6)-Cd8a^tm1Mak/4Dcr

Stock number: 004139
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

The spontaneous lupus erythematosus-like autoimmune syndrome of BXSB/MpJ males carrying Yaa is accelerated in the absence of CD8A, causing a mean survival of approximately 20 weeks instead of 30 weeks.

Detailed description

BXSB/MpJ inbred males (Stock No. 000740) develop a spontaneous lupus erythematosus-like autoimmune syndrome in which mortality starts at approximately 13 weeks of age with 50% lethality by approximately 30 weeks and 76% lethality by approximately 40 weeks. BXSB/MpJ inbred females develop a greatly attenuated form of autoimmune disease. Ablation of CD8 accelerates mortality from the SLE-like autoimmune disorder such that the survival curve for Yaa carrying males of this strain, homozygous for Cd8a^tm1Mak, shows mortality as early as 12 to 15 weeks of age and a mean survival of approximately 20 weeks of age (McPhee et al., 2011). This is a less severe disease acceleration than is caused by ablation of B2m in Yaa carrying BXSB/MpJ males, in which the mean survival is only 18 weeks of age.

Development

This strain was generated in the laboratory of Dr. Derry Roopenian by backcrossing the Cd8a^tm1Mak allele from a C57BL/6J congenic background (stock number 002665) onto the BXSB/MpJ background for 17 generations before sibling intercrossing to homozygosity.

Allele

Symbol: Cd8a^tm1Mak
Name: targeted mutation 1, Tak Mak
MGI accession ID: MGI:1857149
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd8a
Marker name: CD8 antigen, alpha chain
Chromosome: 6
Strain of origin: 129S2/SvPas
Molecular note: A neomycin resistance gene was inserted into exon 1. Flow cytometry analysis on thymus and lymph node cells derived from homozygous mice confirmed that no detectable encoded protein was expressed on the cell surface.

Allele

Symbol: Yaa
Name: accelerated autoimmunity and lymphoproliferation
MGI accession ID: MGI:1856277
Generation method: Spontaneous
Marker symbol: Yaa
Marker name: accelerated autoimmunity and lymphoproliferation transposition
Chromosome: Y
Strain of origin: SB/Le
Molecular note: An approximately 4 MB region of the X chromosome that includes at least 13 known genes (spanning from Ofd1 to Mid1) was translocated to the Y chromosome adjacent to the pseudoautosomal region. Increased RNA expression of Msl3, Tlr7, Tmsb4x and Rab9 was detected in follicular B cells.