Tim Mohun: Projects

DMDD (Deciphering the Mechanisms of Developmental Disorders)

The DMDD programme is a systematic study of embryonic-lethal mouse knockout lines, and provides a database of high-resolution image data and phenotypes.

The programme is funded by the Wellcome Trust, and aims to identify critical genes for embryo development and survival.

About the Programme

The DMDD's mission is to further understanding of developmental disorders through the study of embryonic-lethal mouse lines. At the heart of the programme is an online database, where all our data is freely available to the biomedical community.

Early analysis of our embryonic-lethal data has suggested links between specific genes and heart defects in the developing embryo. Our goal is that the scientific community exploits the database to the full, sparking new areas of study or broadening existing research into the genetic basis of developmental disorders.

To facilitate future research, our mouse lines are archived and are available via Infrafrontier.

Imaging 

DMDD is pioneering the use of High Resolution Episcopic Microscopy (HREM) in studies of embryonic lethal mouse lines. This technique produces images of incredibly high resolution through the entire embryo. It means that embryos with a lethal gene mutation can be compared to their wild-type siblings in exquisite 3D detail.

A video comparing an embryo with a knockout of the embryonic-lethal gene Psat1 (right) and its wild-type litter-mate (left).

Phenotyping

Embryo images are studied by expert anatomists, who identify abnormalities in a range of organs and tissue structures. Placentas are also studied, in order to understand the effect of embryonic lethal gene knockouts on placental development.

Online database

All DMDD data is available to view and study online via our database, which is an ever-expanding resource for developmental biologists and clinicians.

Embryo images can be searched by gene, phenotype or tissue, enabling researchers to identify previously unstudied genes or phenotypes relevant to their own work. A library of normal embryos is also provided for comparison.

Contributing institutions

DMDD is an international consortium of scientists who, together, have expertise in almost every aspect of embryo development. 

At the Wellcome Trust Sanger Institute, the Mouse Phenotyping Group produces embryos from lethal knockout gene lines and initially checks for gross morphological abnormalities. The Vertebrate Genetics and Genomics Group studies the RNA transcript of these embryos, to understand the difference in gene expression between a normal embryo and one with a gene mutation.

The Francis Crick Insitute uses HREM to take high-resolution images of embryos, and is continually developing the database and web interface.

At the Medizinische Universität Wien, expert anatomists study the HREM images and identify tissue and organ abnormalities that may have resulted from the embryonic-lethal gene knockouts.

Oxford University also phenotype embryos and are developing a method for CT scanning of embryos.

The UCL Institute of Child Health studies the cardiovascular system of the embryos in detail, and provides additional phenotype information.

King's College London considers embryos that die at or shortly after the time of birth. They examine the neural tissue in the brain and spinal cord using immunohistochemistry to understand the cause of perinatal death.

The Babraham Institute studies placentas from embryonic-lethal embryos using histology, in order to understand the role of the placenta in embryo development.

The Institute of Genetics and Molecular Medicine have led the emouseatlas project, which provides an online database for normal mouse embryo anatomy and gene expression. Their detailed and annotated images of mouse embryos are a valuable reference point for comparing with embryos from embryonic-lethal lines.

Contact: contact@dmdd.org.uk