Research Project

Automated Three-dimensional Phenotyping of Mouse Embryos

Lead Investigator(s): 
Mark Henkelman
Funding: 
$1.5 M
Institution: 
Hospital for Sick Children
Start Date: 
April 1, 2008
End Date: 
March 31, 2010

Summary

As the genetic origins of common diseases emerge, the role of genomic research in mice, a model organism which shares about 99% of its genetic sequence with humans, will become increasingly important in informing and directing investigations in humans.  Understanding the functions of genes and their networks in mice will undoubtedly translate to new insight into the development of novel treatments of many human diseases.
 
This internationally-funded project, led by Dr. Mark Henkelman, aims to systematically mutate all mouse genes, about 25,000, one at a time, resulting in 25,000 genetically unique mice which may then be compared with normal, or wild-type, animals to uncover the structural and/or physiological differences caused by the mutation.  In order to accurately and completely characterize the mutant mice, the project is developing new 3D MRI imaging technology and computational analysis methods to efficiently and with high resolution visualize differences in the range of tissues to be analyzed.
 
By comparing images of the unique gene-modified mice with reference images from normal mice, the team hopes to discover new genes and define their developmental and physiological function, ultimately transfering this knowledge to the study of human disease.
 
Within two years, the project team will have determined the best way to image mouse embryos such that the differences may be easily identified by a computer. This technology will become available to researchers across Canada and as a service to genomics research facilities abroad. Moreover, the project team intends to establish a company in Ontario that will provide image-based phenotyping to the rest of the world.

Dr. Mark Henkelman is a Professor at the University of Toronto, Director of the Mouse Imaging Centre (MICe) and a Senior Scientist at the Hospital for Sick Children.

Significant Outcomes to Date

  • Dr. Mark Henkelman was awarded the Canadian Cancer Society Robert L. Noble Prize for outstanding achievements in cancer research in 2008.
  • The project has built coils for high-resolution, good contrast images of mouse embryos, increasing the signal-to-noise ratio by approximately 2.5-fold compared to that of standard coils used for brain imaging. A modular 16-coil array, using these new coils, is currently being tested.