Skip to main content
Dryad

Decreased content of ascorbic acid (vitamin C) in the brain of knockout mouse models of Na+, K+- ATPase-related neurologic disorders

Abstract

Raw data, a2Ca3-dKO phenotype and dystonic spell of a3-HT

We found brain haemorrhage phenotype of Atp1a2 and Atp1a3 doule knockout (α2α3-dKO) foetuses. Here we present two kinds of α2α3-dKO line, α2-Nα3-dKO andα2-Cα3-dKO, both show brain haemorrhage upon birth. They were similar to that of homozygous knockout of the gene encoding ascorbic acid (ASC orNvitamin C) transporter, SVCT2 (SVCT2-KO).  We made SVCT2-knockout mouse line by CRIPR/CAS9 method. We present SVCT2-KO, showing brain hemorrage as α2α3-dKO. The α2α3-dKO and SVCT2-KO brain showed significantly decreased level of ASC compared with the wild-type (WT) and single knockout (here, raw data). We found that the ASC content in the basal ganglia and cerebellum was significantly lower in the adult Atp1a3 heterozygous knockout mouse (α3-HT) than in the WT (here, raw data). We did not observe increased oxidative stress in them (here raw data). Interestingly, we observed a significant decrease in the ASC level in the basal ganglia and cerebellum of α3-HTin the peripartum period, during which mice are under physiological stress(here, raw data). Here, we show dystonic spell of α3-HT in peripartum. These observations indicate that the α2 and α3 subunits independently contribute to the ASC level in the foetal brain and that the α3 subunit contributes to ASC transport in the adult basal ganglia and cerebellum. We propose that decreases in ASC levels may affect neural network development and are linked to the pathophysiology of ATP1A2- and ATP1A3-related neurologic disorders.