GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.

ABSTRACT: The cellular etiology of seizures in CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), remains elusive. Given that Cln2R207X/R207X mice display fatal spontaneous seizures and an early loss of several cortical GABAergic interneuron populations, we hypothesized that these 2 events might be causally related. To study the cell-autonomous effects of interneuron-specific TPP1 deficiency, we first generated transgenic mice expressing loxP-flanked lysosomal membrane-tethered TPP1 (TPP1LAMP1 mice) on the Cln2R207X/R207X genetic background, and then crossed TPP1LAMP1 mice with Vgat-Cre mice. These Vgat-Cre; TPP1LAMP1 mice accumulated storage material in cortical and striatal interneurons. Vgat-Cre; TPP1LAMP1 mice al

SUBMITTER: Takahashi K 

PROVIDER: S-EPMC12513480 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature