RT Journal Article SR Electronic T1 Upregulation of RCAN1 causes Down syndrome-like immune dysfunction JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 444 OP 454 DO 10.1136/jmedgenet-2013-101522 VO 50 IS 7 A1 Katherine R Martin A1 Daniel Layton A1 Natalie Seach A1 Alicia Corlett A1 Maria Jose Barallobre A1 Maria L Arbonés A1 Richard L Boyd A1 Bernadette Scott A1 Melanie A Pritchard YR 2013 UL http://jmg.bmj.com/content/50/7/444.abstract AB Background People with Down syndrome (DS) are more susceptible to infections and autoimmune disease, but the molecular genetic basis for these immune defects remains undetermined. In this study, we tested whether increased expression of the chromosome 21 gene RCAN1 contributes to immune dysregulation. Methods We investigated the immune phenotype of a mouse model that overexpresses RCAN1. RCAN1 transgenic (TG) mice exhibit T cell abnormalities that bear a striking similarity to the abnormalities described in individuals with DS. Results RCAN1-TG mice display T cell developmental defects in the thymus and peripheral immune tissues. Thymic cellularity is reduced by substantial losses of mature CD4 and CD8 thymocytes and medullary epithelium. In peripheral immune organs T lymphocytes are reduced in number and exhibit reduced proliferative capacity and aberrant cytokine production. These T cell defects are stem cell intrinsic in that transfer of wild type bone marrow into RCAN1-TG recipients restored medullary thymic epithelium and T cell numbers in the thymus, spleen and lymph nodes. However, bone marrow transplantation failed to improve T cell function, suggesting an additional role for RCAN1 in the non-haemopoietic compartment. Conclusions RCAN1 therefore facilitates T cell development and function, and when overexpressed, may contribute to immune dysfunction in DS.