Ank2-flox Mouse

ANK2, encoding ankyrin-B, is a cytoskeletal scaffolding protein that recruits membrane proteins into specialized membrane domains. It is involved in multiple biological processes, with its role in neuronal development and function being of particular significance. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying ANK2 [2,3,4].

ANK2 loss-of-function (LoF) variants in humans are associated with a broad neurodevelopmental disorder (NDD), including intellectual disability, autism spectrum disorders, and early-onset epilepsy. hiPSC-derived neurons with heterozygous LoF of ANK2 show hyperactive and desynchronized neuronal networks, increased somatodendritic structures, and impaired axon initial segment (AIS) plasticity [1]. In mouse models, prenatal deletion of Ank2 in cortical excitatory neurons and oligodendrocytes (Ank2-/-:Emx1-Cre) leads to severe spontaneous seizures, increased mortality, hyperactivity, and social deficits, along with network hyperexcitability and hypersynchrony. Quantitative proteomic analysis reveals synaptic proteome alterations [3]. Mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) display ASD-related behavioral abnormalities and juvenile seizure-related death, with increased neuronal excitability due to decreased Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels in the AIS, which can be rescued by the Kv7 agonist retigabine [4].

In conclusion, ANK2 plays essential roles in neuronal development and network function. Studies using KO and CKO mouse models have significantly contributed to understanding its role in neurodevelopmental disorders, such as autism spectrum disorders and epilepsy. These findings provide insights into the molecular mechanisms underlying these diseases, which may facilitate the development of new therapeutic strategies.