In this paper, Dyment et al detail a new mouse for the study of Dravet syndrome modeled after a patient mutation. This particular mutation (H939R) does not result in the typical haploinsufficiency where Nav1.1 sodium channel levels are reduced, but rather appears to affect the function of one copy of the sodium channel. Consistent with other models of Dravet, these mice have spontaneous and heat-induced seizures, delayed growth, and increased mortality. Significant alterations in the electrical currents from hippocampal neurons indicate that sodium channels are not working properly in these mice carrying the H939R mutation. These mice also have reduced numbers of specific neuron populations, some of which have been reported in other models. However, they report for the first time a reduction in interneurons expressing vesicular acetylcholine transferase, implicating a potential role for acetylcholine in Dravet syndrome. The researchers also compared neurons derived from induced pluripotent stem cells from the original individual with Dravet and an unaffected individual, and found similar results in the electrical properties to those observed in the mouse model.
As discussed in other research reviews, there are now many mouse models of Dravet syndrome. Most of these models display a range of phenotypes, that can vary based on the type of mutation in the SCN1A gene and the strain of mouse, as well as the age and gender of the mice used in the studies. While a lot of variation in the results can make drawing conclusions a bit more difficult, it is also important to remember the amount of variability in the human population with Dravet, and recognize that exploring the different animal models of Dravet syndrome may help find treatments that work for broader patient populations.