(Tatsukawa et al. 2018) When scientists first started studying Scn1a in mice, their only option was to generate a mouse family that had a human Dravet-like mutation (that rendered the gene non-functional) or not. That is, the mice either had the mutation in all of their cells, or they didn\’t. With new techniques, scientists are now able to generate mice that have the mutation in only particular cells, which helps them identify exactly which types of cells are involved in the Dravet syndrome clinical picture.
In previous studies, Scn1a has been found to be expressed in parvalbumin-expressing neurons (PV+). Parvalbumin is a protein made by cells (such as the GABAergic interneurons suspected to play a significant role in Dravet syndrome) for use in calcium signaling. To determine the effects of Scn1a mutations on these particular cells, the authors compared two complex mouse models: One that harbored a mutation in PV+ cells only, and one that harbored a mutation in somatostatin (SST)-expressing cells. They found that, as predicted, the mice with mutations in the PV+ cells had significant behavior, social issues, and impaired spatial memory, while the mice with similar mutations in SST+ cells did not have behavioral abnormalities. The authors conclude that changes in PV+ inhibitory interneurons due to Scn1a mutations are the basis for the behavioral issues, autistic characteristics, and cognitive decline seen in the mice.