Brain Imaging – Mouse Models of Dandy Walker Malformation (DWM), Chiari Malformation and hydrocephalus

The underlying disruption in development that leads to these important pediatric diagnoses are largely not understood. Once genes are identified the Millen Lab uses numerous transgenic technologies to generate mouse models of these disorders, creating mice that specifically harbor gene mutations similar to those observed in humans. Once these mutant mice are generated, we can study multiple stages of embryos and post-natal mice to determine when development goes awry. Central to this analysis is development of methodologies to quantitate the developmental changes.  For example: DWM is a malformation of the cerebellum, but also the posterior fossa, since an enlarged posterior fossa is a pathognomonic feature of DWM. To determine if brain and skull size are normally tightly correlated in mice, Dr. Millen’s group conducted both MRI and mCT analysis on multiple wild-type mice and developed methods in collaboration with Drs. Brian Nieman and Henkelman at the University of Toronto Mouse Imaging Center. These neuroimaging studies now serve as a baseline to quantitatively assess posterior fossa size in mouse with abnormalities of the posterior fossa (back of skull) such as Chiari Malformation and hydrocephalus.

Mouse Model image


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