Science for Health
19 March 2013
A consortium of institutions, led by researchers from NIMR, has been granted a Wellcome Trust Strategic Award to identify genes essential for mouse development and the origins of developmental diseases and birth defects in humans.
Biologists seek to understand the functions of all the genes in our genome and to discover which of them cause inherited disease. Around one in forty infants in Europe are born with either inherited or spontaneous defects in one or more genes, causing birth defects. Some defects are so severe that they result in miscarriage or stillbirth.
The International Knockout Mouse Consortium is a global 10-year project that is testing gene function in mice by systematically knocking out each gene. This helps to identify genes that contribute to disease. The IKMC has also shown that around one third of the 21,000 genes in the mouse genome are vital for normal development: without them the mouse does not develop beyond the embryonic stage or dies as a newborn. These mutants therefore can't be studied as adults. They are however valuable to developmental biologists seeking genes that are essential for embryogenesis and could be important for clinicians, identifying genes in which mutations contribute to congenital disorders.
The Wellcome Trust has funded a new programme of research dedicated to studying these embryonic lethal mouse mutations. Deciphering the Mechanisms of Developmental Disorders (DMDD) is a consortium that brings together developmental biologists and clinicians from across the UK in a common effort to identify these genes and to begin to study why their mutation has such profound effects on embryo development and survival.
Led by Tim Mohun (pictured), in NIMR’s Division of Developmental Biology, the core of the work draws on his embryo imaging research but the programme also draws on expertise in mouse genetics, imaging and embryology in several other institutions (Sanger Institute, Oxford University, Babraham Institute, Edinburgh University, Kings College London, MRC Harwell, University of Vienna). Starting in spring 2013, the programme will use high-resolution 3D imaging of embryos that do not survive in order to identify and catalog the structural developmental abnormalities that result from the removal of each gene, along with detailed descriptions of their physical characteristics. The resulting database will make all this wealth of data freely and readily available to the biomedical community via a dedicated website.
By using the latest 3D imaging techniques, DMDD will screen the external and internal structure of mutant embryos, cataloguing the range and severity of the abnormalities that are detected.
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA