A murine model lacking Lyst recapitulates Chediak-Higashi syndrome with an earlier-onset neurodegenerative phenotype.

ABSTRACT: Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder caused by pathogenic variants in the lysosomal trafficking regulator (LYST) gene and characterized by significant immunological and neurological impairment. Current mouse models do not replicate the early-onset neurological symptoms of patients. We develop and characterize a CHS model lacking the Lyst gene (ΔLYST-B6) using CRISPR-Cas9. The ΔLYST-B6 mouse exhibits key CHS features, including partial oculocutaneous albinism, prolonged bleeding, and enlarged intracellular granules. Molecular analyses confirm LYST deficiency, with reduced Lyst mRNA and protein levels across various tissues. Histological examination reveals progressive cerebellar Purkinje cell loss and axonal degeneration in peripheral nerves. Importantly, t

SUBMITTER: Greene S 

PROVIDER: S-EPMC12274407 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature