MRL-IPR/IPR mice please explain your findings - somber

[ArchivalUser]

MRL-IPR/IPR mice are useful biomedical research models because of their increased susceptibility to autoimmune disease. These mice are charcterized by a defect in the FAS Gene and a marked increase in T-Lymphocyte accumulation as compared with wild-type animals. Based on these characteristics, which of the following is the most likely cause of the increased susceptibility of these mutants to autoimmune disease
A-Decreased cell-cycle transit time for activated T-Lymphocytes
B-Decreased dependence on antigen-presenting cells for T-lymphocyte activation
C-Decreased responsiveness to clonal deletion signals in the thymic cortex
D-Increased responsiveness of mature T lymphocytes to antigenic stimulation
E-Increased thymocyte precursor proliferation in the bone marrow
F-increased thymocyte proliferation rate in the thymic cortex

[ArchivalUser]

maybe if we found out what the "FAS" gene is for it would be easier to tackle? Does anyone have a clue?

[ArchivalUser]

I think the answer is C.

MRL-lpr/lpr mice are FAS deficient. "FAS" can induce appotosis.

The following is what I have found in the web:

Autoantibodies directed against dsDNA are found in patients with systemic lupus erythematosus as well as in mice functionally deficient in either Fas or Fas ligand (FasL) (lpr/lpr or gld/gld mice). Previously, an IgH chain transgene has been used to track anti-dsDNA B cells in both nonautoimmune BALB/c mice, in which autoreactive B cells are held in check, and MRL-lpr/lpr mice, in which autoantibodies are produced. In this study, we have isolated the Fas/FasL mutations away from the autoimmune-prone MRL background, and we show that anti-dsDNA B cells in Fas/FasL-deficient BALB/c mice are no longer follicularly excluded, and they produce autoantibodies. Strikingly, this is accompanied by alterations in the frequency and localization of dendritic cells as well as a global increase in CD4 T cell activation. Notably, as opposed to MRL-lpr/lpr mice, BALB-lpr/lpr mice show no appreciable kidney pathology. Thus, while some aspects of autoimmune pathology (e.g., nephritis) rely on the interaction of the MRL background with the lpr mutation, mutations in Fas/FasL alone are sufficient to alter the fate of anti-dsDNA B cells, dendritic cells, and T cells

http://www.jimmunol.org/cgi/content/full/167/4/2370



These death activators include:
1) Tumor necrosis factor-alpha (TNF-α ) that binds to the TNF receptor;
2) Lymphotoxin (also known as TNF-β ) that also binds to the TNF receptor;
3) Fas ligand (FasL), a molecule that binds to a cell-surface receptor named Fas (also called CD95).

[ArchivalUser]

Fas is a cell surface receptor, which when activated initiates the sequence of events that lead to apoptosis. In MRL-lpr/lpr mice Fas is defective, so the competency for apoptosis may be reduced.
Clonal deletion in the thymus by apoptosis is involved in purging the immune system of self-reactive T lymphocytes (negative selection)- those responsible for autoimmune disease. Developing B and T lymphocytes that do not express functional antigen receptor fail to receive a positive signal and die via apoptosis (death by neglect), whereas lymphocytes bearing self-reactive antigen receptors undergo apoptosis in response to a death signal from neighboring cells (negative selection).
I hope this explains the answer.

[ArchivalUser]

It does thanks for your time