Great news! We have mice! It took over a year but Dr. Swanson was able to produce a mouse with Katie's same mutation and then breed it, so now he has lots of Katie mice.
One of the first tests they conducted was to have a normal (wildtype) mouse and a Katie mouse walk along the edge of a cage. He explains below about the struggles the mutated mouse has which just blows me away! I can't get over that these mice are actually showing a symptom in movement like Kate has. So incredible! See pictures below.
Also, if you haven't seen my 2 minute video here it is: http://bit.ly/2C78BsP
From Dr. Swanson:
"Figuring out the cellular and circuit rearrangements that result from rare genetic variants like Katie's is challenging and requires the use of model systems like mice. Mice are by far the most common animal model for human genetic disorders in part because their genome can be modified reliably with powerful editing technology. We introduced into mice the same nucleotide variant that Katie has in her GRIK2 gene. We call the this new strain "GluK2(A657T)" mice. The A and T simply refers to the change in amino acid structure (A/alanine to T/threonine) of the GluK2 protein that results from the GRIK2 genetic variation. We expect the amino acid change to fundamentally alter the signaling of kainate receptors that contain the GluK2 protein, which are important for early development of the central nervous system.
What were we hoping to see in the GluK2(A657T) mice? Most importantly, we were hoping that the mice would show some of the same behaviors that Katie exhibits. If this occurs, then we say the mouse strain has "face validity" - that is, it actually does model some aspects of the human disorder. We always have to keep in mind that mice are not humans, and mouse brains are not nearly as complex and powerful as human brains. Not all mouse models show face validity for their associated human disorders. Thankfully, many mouse models do recapitulate features of human genetic disorders, which is what in part makes them powerful research tools. We can use behavioral tests to guide us to the parts of the brain that can be most effectively analyzed for changes in nervous system development.
The first set of data we have obtained from the GluK2(A657T) mice suggest that they do indeed have face validity for at least one aspect of Katie's genetic disorder. These pictures show that the GluK2(A657T) mice have a difficult time performing a routine task - walking along the edge of their cage. Walking on the "ledge" requires balance, muscle strength, and control of fine and coarse muscles. The fact that the GluK2(A657T) mice perform poorly on this simple task suggests that they have a motor disorder known as "ataxia" - like Katie.
We are just at the beginning of this analysis but are very encouraged by these data. Our hope and expectation is that the GluK2(A657T) mice will lead us to new insights into the neurodevelopmental basis of Katie's disorder as well as in other children with similar genetic disruptions."
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