PgmNr M254: The DMDD programme: an online database of embryonic lethal mouse gene mutations.

Authors:
Jacqui White 1 ; and the DMDD Consortium 1,2,3,4,5,6,7,8


Institutes
1) The Francis Crick Institute, London, UK; 2) Wellcome Trust Sanger Institute, Cambridge, UK; 3) Babraham Institute, Cambridge, UK; 4) King's College London, London, UK; 5) University of Oxford, Oxford, UK; 6) MRC Human Genetics Unit, Edinburgh, UK; 7) Medizinische Universität Wien, Vienna, Austria; 8) UCL, London, UK.


Abstract:

The DMDD programme (Deciphering the Mechanisms of Developmental Disorders) provides a free online database of embryonic-lethal mouse gene knockouts and their related phenotypes. This Wellcome Trust-funded research programme is a unique and expanding resource for both developmental biologists and clinicians, offering a novel way to study embryo development and the possible aetiology of human developmental disorders.

Embryos are comprehensively imaged using high-resolution episcopic microscopy (HREM), allowing them to be examined in 3D at an unprecedented resolution. A team of expert anatomists then scores structural abnormalities in tissue organisation and organ structure using a standardised phenotype ontology. Embryo placentas are examined by histology to assess the impact of gene mutation on placental development, while for perinatal deaths the neural tissue in the brain and spinal cord are examined using immunohistochemistry.

The DMDD database (http://dmdd.org.uk) is continually updated with new results and currently holds data from over 300 embryos, comprising nearly 3 million images. Each embryo can be viewed in a stack viewer at full (3 micron) resolution and tools are provided to allow rapid navigation in all 3 orthogonal planes. All phenotype information is available in tabular form and is also identified within the appropriate images. Data is presented both by embryo and by mouse line, enabling both the severity and penetrance of each phenotype to be assessed. Image data from different embryos can be viewed side by side and a reference library of datasets from normal embryos at different stages of development is also available for comparison.

Powerful search functions increase the potential of the database, enabling users to identify relevant data by gene, tissue or phenotype. All data is available for download on request, while mouse lines of interest can be obtained from the European Mutant Mouse Archive (EMMA) for further study.

DMDD data has already suggested links between specific genes and abnormal embryonic heart structure, and shed light on the importance of gene mutations on the developing placenta. The database offers a wealth of information to be explored by those researching specific genes or developmental disorders, and has the potential to identify previously unknown links between groups of genes or phenotypes.