Disease relevance of Sle1c

• Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein [1].
• A chronic graft-vs-host disease model also showed that Sle1c produces significantly more autoreactive B cells than B6 controls, and that this phenotype maps to two regions excluding the Cr2 gene [2].

High impact information on Sle1c

• To determine whether the New Zealand White (NZW)-derived Sle1c interval would interact with New Zealand Black (NZB) genes to result in enhanced autoimmune phenotypes, NZB mice were bred with B6 or B6.Sle1c congenic mice and approximately 20 female offspring were selected from each breeding for longitudinal study [3].
• The Sle1c lupus susceptibility interval spans a 7-Mb region on distal murine chromosome 1 [3].
• These mice differ only at the Sle1c locus at which they have either a NZB/B6 or NZB/NZW genotype [3].
• Mixed bone marrow chimera demonstrated that the increased activation, proliferative response, and reduced regulatory T cell compartment were intrinsic to Sle1c-expressing CD4(+) T cells [2].
• Telomeric Sle1c is associated with abnormal B cell responses to subthreshold stimulation with anti-IgM and C3d and with decreased T-dependent humoral immune responses [2].

Anatomical context of Sle1c

• We have also found that Sle1c was associated with the production of histone-specific autoreactive CD4(+) T cells, which correlated with higher activation and proliferative responses, and a reduction in the CD4(+)CD25(+)CD62L(+)forkhead/winged helix transcription factor gene (Foxp3(+)) compartment [2].
• Moreover, Sle1a and Sle1c were associated with a significantly reduced level of CD4(+)CD25(+) regulatory T cells that precedes autoantibody production, suggesting a causal relationship with the generation of autoreactive T cells [4].

References