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Original Article
Upregulation of RCAN1 causes Down syndrome-like immune dysfunction
  1. Katherine R Martin1,
  2. Daniel Layton2,
  3. Natalie Seach2,
  4. Alicia Corlett1,
  5. Maria Jose Barallobre3,
  6. Maria L Arbonés3,4,
  7. Richard L Boyd2,
  8. Bernadette Scott5,
  9. Melanie A Pritchard1
  1. 1Department Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  2. 2MISCL, Monash University, Clayton, Victoria, Australia
  3. 3Center for Genomic Regulation (CRG), UPF, and Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
  4. 4Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Barcelona, Spain
  5. 5Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Clayton, Australia
  1. Correspondence to Dr Melanie Pritchard, Department Biochemistry and Molecular Biology, Monash University, Wellington Rd, Clayton, VIC 3800, Australia; melanie.pritchard{at}


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.

  • Immunology (including allergy)
  • Molecular genetics

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