Mutation in <i>Wdr45</i> leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model.

ABSTRACT: Beta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in WDR45. Currently, there is no cure or disease altering treatment for this disease. This is, in part, due to a lack of insight into early phenotypes of BPAN progression and WDR45's role in establishing and maintaining neurological function. Here we generated and characterized a mouse model bearing a c52C > T BPAN patient variant in Wdr45. We show this mutation ablates WDR45 protein expression and alters autophagy in the brain. Behavioral analysis of these mice revealed characteristic signs of BPAN including cognitive impairment, hyperactivity, and motor decline. We show these behaviors coincide with widespread glial ac

SUBMITTER: Meyerink BL 

PROVIDER: S-EPMC11907653 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature