Researchers aim to use cellular imaging to determine how Down’s syndrome affects stem cells in the developing brain in a new animal model, and then determine how altered stem cell development relates to the behavioral abnormalities that the animals exhibit following birth.
A mouse model referred to as “Ts65Dn” is an exact genetic replica of human Down’s syndrome and exhibits behavioral abnormalities after birth. These mice are difficult to breed in the laboratory. With the Down’s syndrome hallmark of three copies of a gene on chromosome 21, and behavioral dysfunctions, the model represents a substantial advantage over the existing “Down’s syndrome-like” mouse model. The two disadvantages of the existing model are that it is an inexact replica and the immediate death after birth of the laboratory mice precludes any behavioral study. However, the existing model has provided evidence that stem cells in the brain do not divide normally during embryonic development. This abnormality delays growth of cells in the brain’s cortex, and compromises neuronal connections between the cortex and the rest of the brain before birth.
With the new Ts65Dn animal model, scientists would be able to confirm these abnormal stem cell findings and their effects on neural connections in an exact genetic animal model replica of the human disease. They also would be able to correlate the brain abnormalities with behavioral dysfunctions in the animals following birth.
To date, with feasibility funding from Dana, the researchers have been able to make progress in breeding the mice. Phase II funding of $100,000 will enable the investigators to complete the breeding of enough mice to conduct their imaging and behavioral studies.
If Phase II is successful, researchers will receive Phase III funding of $100,000 to use multi-photon microscopy to determine the effects of aberrant stem cell division on brain cell growth and connectivity, and relate these findings to the animals’ abnormal behaviors.
Significance: Cellular imaging in this animal genetic replica of human Down’s syndrome could provide vital information on how this devastating developmental disorder occurs in the brain.