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The consequences of over expression of RCAN1 on the brain and immune system and its implications for Down Syndrome

posted on 14.02.2017, 00:13 by Martin, Katherine Rosemary
Down Syndrome (DS) is caused by trisomy of HSA21 in humans and is the most common autosomal aneuploidy, occurring in about 1 in 700 live births. DS is a major genetic cause of intellectual disability and is characterised by a reduction in the size and altered morphology of the brain. DS is also associated with immunological dysfunction, with sufferers being more susceptible to infection and having a higher incidence of both autoimmune disorders and haematological cancers. Many of the immune deficits observed in DS are T cell dependent, with T cell development and function adversely affected. One of the genes located on HSA21 that is believed to contribute to some of the DS phenotypes is Regulator of Calcineurin 1 or RCAN1. In order investigate the effects of over expression of RCAN1 on the brain and immune system we used mice over expressing RCAN1. In this study we found that over expression of RCAN1 in the brain resulted in multiple defects in the formation, structure and function of the hippocampus and these structural abnormalities were accompanied by cognitive impairments. We also reveal that over expression of RCAN1 in mice replicates a subset of the immune deficiencies observed in DS. Specifically, RCAN1-TG mice exhibited impaired T cell development and maturation within the thymus as well as T cell functional deficits characterised by a reduced proliferative capacity and aberrant cytokine production. In a separate study we found that increased levels of RCAN1 provided protection against ischaemic damage (stroke) in the brain by decreasing neuronal cell death and reducing inflammation. Based on the results presented in this study we have demonstrated that RCAN1 plays an important role in the development and function of the neurological and the immune systems and when over expressed, may be a key contributor to the abnormal phenotypes intrinsic to DS, yet protective in stroke.


Principal supervisor

Melanie Pritchard

Additional supervisor 1

Bernadette Scott

Year of Award


Department, School or Centre

Biochemistry and Molecular Biology

Campus location



Doctor of Philosophy

Degree Type



Faculty of Medicine Nursing and Health Sciences