Department of Biomedicine, University of Aarhus
My lab pioneered the generation of a mouse model for ATP1A3-related disorders, harboring the D801Y mutation in the ATP1A3 gene. The α3+/D801Y mice phenocopy many symptoms associated with Alternating Hemiplegia of Childhood (AHC). We concluded that the D801Y is a loss-of-function mutation for Na+/K+ exchange, but are effectively gain-of-function in that the mutant pumps engage full time in proton import, which possibly accounts for the scarcity and severity of these de novo gene alterations and the apparent lack of nonsense mutations (resulting in haploinsufficiency) in the ATP1A3 patient group.
We further generated a mouse model for Familial Hemiplegic Migraine type 2, harboring a disease-mutation in the ATP1A2 gene, which provided a link between the female sex hormone cycle and the glutamate system and a link to co-morbid psychiatric manifestations of FHM2.