Ask Jeff: The Mouse Expert Replies

You may recall that back in September we asked if anyone had questions about the PKAN knock-in mice for our resident mouse wrangler, Jeff. We had one curious dad who submitted some very interesting questions (and a few amusing ones that gave our team a good laugh). So without further ado, here are some answers:

Q1. Is the defect identical on both genes or are there two different ones mixed together?

The mutation in both of their PANK2 genes is the same. This allows us to have consistency in their behavior. One can imagine that if one particular mutation is more damaging to the PANK2 gene than another that would make things quite confusing for testing.

Q2. How do you ensure there are no other genetic spontaneous or inherited conditions causing symptoms?

All mice are bred on a specific genetic “background”. Basically, that means that they’re all a standard breed of mouse, in the same way that Jack Russell terriers are a standard breed of dog. The mice are identical except for the PKAN-causing mutations. To make sure they stay that way, we periodically order certified mice of that breed from a company and mate them with our colony. That allows us to minimize any outside spontaneous genetic conditions.

Q3. How do you get your mice to fall over backwards if they have four legs?

When we evaluate humans with PKAN, we measure their balance and coordination by having them do tests like walking a short distance or standing with their eyes closed. However, with PKAN mice, we use a different method called the rotarod performance test. A rotarod is a rotating cylinder as seen in the image below. Basically, the mice are placed on the rotarod and we see how well they’re able to stay perched on that cylinder. Mice with movement disorders, like PKAN, tend to fall off quickly.
genericrotarod
Image courtesy of www.measuringbehavior.org

Q4. Do the mice get headphones in the MRI? What music do you play them?

We don’t use MRIs to evaluate the mice’s brain, but if we did, I imagine the “Mighty Mouse” theme song would be a favorite :)