Males of this strain carry the BXSB-derived Yaa mutation on the Y chromosome.
The Y-linked autoimmune accelerator locus (Yaa) on the Y chromosome of BXSB inbred male mice is the result of a duplication of an ~4 Mbp telomeric segment near the pseudoautosomal region of the X chromosome onto the Y chromosome. The duplicated segment contains 19 genes, including toll-like receptor 7 (Tlr7) and phosphoribosyl pyrophosphate synthetase 2 (Prps2). BXSB males have the mutant Yaa-containing Y chromosome, and are a model for a severe form of systemic lupus erythematosus (SLE). Their spontaneously arising autoimmune disease is characterized by the robust development of follicular T cells and germinal centers. Marginal zone B cells are depleted in BXSB-Yaa mice and a dramatic increase in number of peripheral monocytes is seen beginning at two months of age. Disease progression is characterized by lymph node and spleen enlargement, hemolytic anemia, hypergammaglobulinemia, anti-nuclear antibodies, and immune complex glomerulonephritis. This leads to morbidity on average of six months of age. BXSB females develop a greatly attenuated form of autoimmune disease; indicating that autoimmune disease acceleration is due to the presence of the Yaa mutation carried on the Y chromosome.
A duplicated copy of the Tlr7 gene is primarily responsible for the autoimmune phenotype attributed to the Yaa mutation. The BXSB-Yaa mouse therefore provides a model for investigating the effects copy number variation of Tlr7 on autoimmune disease. Therapeutic treatment of BXSB-Yaa mice with an anti-Type I interferon receptor antibody attenuates their autoimmune disease; indicating that Type I interferon signaling involved is in the pathogenesis of this disease.
The most suitable control animals are sex-matched, autoimmune disease-resistant BXSB.B6-Yaa+ consomic males carrying the C57BL/6-derived Y chromosome in place of the BXSB-derived mutant Yaa-containing Y chromosome. BXSB.B6-Yaa+ consomic mice (backcrossed to BXSB/MpJ inbred females for at least 40 generations) are described and available at The Jackson Laboratory as Stock No. 021330.
A note on outcrossing BXSB males with other inbred females: similar autoimmune disease acceleration occurs in males (but not in females) from an outcross of BXSB males to NZB females. Acceleration does not occur in offspring of the reciprocal cross. The same effect of Yaa is seen in offspring of outcrosses to strains SJL, C57BL/6, and AKR.
In addition, BXSB males lacking the interleukin 21 receptor (BXSB-Yaa/Il21r-/- or BXSB-Yaa/Il21-/-) are highly resistant to disease and are therefore a model for investigating the role of interleukin 21 in disease pathogenesis. Populations of regulatory CD8+ and potentially natural killer cells are also actively retarding disease in this model; making them useful to investigate the roles of such regulatory cells in autoimmune disease.
|Allele Name||accelerated autoimmunity and lymphoproliferation|
|Allele Synonym(s)||Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw|
|Gene Symbol and Name||Yaa, accelerated autoimmunity and lymphoproliferation transposition|
|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.|
This is an inbred strain. Males carry the BXSB-derived Yaa mutation on the Y chromosome. To maintain the live inbred colony, unaffected females (+/+) may be bred with affected males (Yaa/Y).
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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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