Related Experiment Videos
The interaction of the xid and me genes
Abstract:
The murine "motheaten" (me) mutation has been bred onto the NFS background and combined with the X-linked immunodeficiency (xid) mutation to investigate the effect of the xid-induced B cell maturational block on the widespread immune dysfunction, high levels of autoantibodies, and early mortality found in the motheaten mice. The xid markedly reduced spontaneous IgM secretion by spleen cells, serum IgM, anti-ssDNA antibodies, anti-bromelain-treated-erythrocyte antibodies, and T cell binding (but not thymocytotoxic) antibodies; however, neither phenotype nor mortality was affected, suggesting that other factors are responsible for early death. Marked expansion of the Ly-1+ B cell pool was prevented by xid in the motheaten mouse leaving only a very small population of sIgM-positive B cells. This failure of non-Ly-1+ B cell development in me/me X xid mice suggests that me/me leads to inhibition of non-Ly-1+ B cells and preferential expansion of Ly-1+ B cells in motheaten mice, perhaps as a result of their high levels of maturation and activation factors.
Insights
The X-linked immunodeficiency (xid) mutation reduced autoantibodies in motheaten mice but did not affect mortality, suggesting other factors cause early death in these mice.
Area of Science:
- Immunology
- Genetics
- Autoimmunity
Background:
- The murine motheaten (me) mutation causes widespread immune dysfunction, autoantibodies, and early mortality.
- The X-linked immunodeficiency (xid) mutation induces a B cell maturational block.
Purpose of the Study:
- To investigate the impact of the xid mutation on the immune dysfunction and mortality in motheaten mice.
- To determine the role of B cell maturation in the pathogenesis of motheaten mice.
Main Methods:
- Breeding the me mutation onto the NFS background and combining it with the xid mutation.
- Analyzing B cell populations, autoantibody levels, and mortality in genetically modified mice.
Main Results:
- The xid mutation significantly reduced IgM secretion, serum IgM, and various autoantibodies (anti-ssDNA, anti-erythrocyte, T cell binding).
- Neither the overall phenotype nor mortality rates were affected by the xid mutation in motheaten mice.
- The xid mutation prevented the expansion of Ly-1+ B cells and resulted in a small sIgM-positive B cell population.
Conclusions:
- The xid mutation ameliorates specific autoimmune features in motheaten mice but does not influence overall mortality.
- The motheaten mutation likely inhibits non-Ly-1+ B cell development and promotes Ly-1+ B cell expansion.
- Factors other than those targeted by xid are responsible for the early mortality observed in motheaten mice.