The role of the imprinted gene Zac in pancreatic development and function

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Diabetes mellitus affects nearly 30 million individuals in Europe, decreasing their life quality and expectancy. People with diabetes are no longer able to control the level of sugar in their blood properly, because the hormone, insulin, which normally does this is produced in inadequate amounts. Diabetes comes in two main forms, type 1 and type 2, but in both cases there is a reduction in the number of the cells, the beta cells in the pancreas, that produce the insulin hormone. The reasons for this are not fully known and, although the original causes may differ in type 1 and type 2 diabetes, similar events may have occurred within the beta cells. This knowledge is essential for the development of novel therapies to preserve adequate beta cell mass and thus prevent or cure diabetes. In this project, we shall be studying the function of one particular gene which has been found to control beta cell number and to cause a form of diabetes when its activity is altered.

Publications

10 25 50
 
Description Based on our understanding of the mechanism by which imprinted genes are epigenetically marked in germ cells, we created a mouse model of the imprinted gene syndrome 6q24 transient neonatal diabetes (6q24 TNDM), which is caused by imprinting defects of the ZAC1/PLAGL1 gene. However, although we were able to generate a molecularly faithful model of 6q24 TNDM, mice with defective imprinting of Zac1/Plagl1 do not demonstrate the cardinal symptoms of 6q24 TNDM, such as neonatal hyperglycaemia and insulin insufficiency.
Exploitation Route Although exploitation routes were established in this project (the European SAVEBETA network and clinical genetic and paediatric endocrinologist collaborations in the UK), the failure of this new mouse model to recapitulate the cardinal symptoms of 6q24 TNDM did not offer obvious exploitation opportunities. Moreover, it was anticipated that our work would establish a general role for Zac1/Plagl1 in control of insulin-producing beta cells, that could be of general benefit to understanding defects in beta cells associated with diabetes or that could be used to develop strategies to preserve beta cell mass in this condition.
Sectors Healthcare

 
Description ESPE Research Fellowship
Amount € 124,000 (EUR)
Organisation European Society of Pediatric Endocrinology (ESPE) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2014 
End 12/2015