Transgenic Mice

The two main types of mice used by our research group for NBIA disorders are “knock-out” and “knock-in” mice. These mice are used to study the effects NBIA disorders may have on different organ systems, the progression of symptoms, and to test potential new treatments or compounds of interest.

PKAN Knock-Out Mice

When we first started studying NBIA disorders, we worked with collaborators at UCSF to develop PANK2 knock-out mice. In order to simulate PKAN patients with a mutation in their PANK2 genes, the PKAN mice had their PANK2 genes artificially knocked out.

As is sometimes the case in mouse models, the PKAN knock-out mice do not exhibit the same findings we see in humans. Specifically, they do not have a significant neurological phenotype or brain iron accumulation. Although they do have some features of PKAN and have been useful for many experiments, with the development of new mouse technology we thought we could make a better mouse model.

PKAN Knock-In Mice

The knock-in mice are currently under development by a company called OzGene. The project is funded by the NBIA Disorders Association (NBIADA). We and the NBIADA worked with OzGene to develop mice that have a specific PANK2 mutation commonly seen in humans. We hope this will better simulate the PKAN phenotype. Using newer technologies, this mouse has several bells and whistles that weren’t available previously. For example, investigators can “turn on” the PANK2 mutation only in specific tissues, such as the liver or the brain, as part of their experiments. The NBIADA funded the development of this mouse and can provide it to PKAN investigators worldwide.

Other NBIA Transgenic Mice

Several other mouse models of NBIA exist. Some have occurred naturally, while others were engineered. Although there are many pitfalls to using mouse models, they remain an invaluable tool in understanding NBIA and testing potential treatments.