Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy.

ABSTRACT: Infantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is similar to congenital cytomegalovirus brain infection and overlaps with type I interferonopathies, suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2^-/- mice using CRISPR/Cas9-mediated genome editing. Rnaset2^-/- mice demonstrate upregulation of interferon-stimulated genes and concurrent IFNAR1-dependent neuroinflammation, with infiltration of CD8⁺ effector memo

SUBMITTER: Kettwig M 

PROVIDER: S-EPMC8586222 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature