biostudies-literatureUnknown19Meyerink BLBeta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in <i>WDR45</i>. 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 <i>WDR45</i>'s role in establishing and maintaining neurological function. Here we generated and characterized a mouse model bearing a c52C > T BPAN patient variant in <i>Wdr45.</i> We show this mutation ablates <i>WDR45</i> 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 acFrontiers in neuroscience1545004https://www.ebi.ac.uk/biostudies/studies/S-EPMC11907653biostudies-literatureMutation in &lt;i&gt;Wdr45&lt;/i&gt; leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model.PMC11907653Aftab SHoward JMRechtzigel MJPatthi PRPilaz LJKaria KSMeyerink BLEdwards ACAaseng ERWeimer JMfalseMutation in &lt;i&gt;Wdr45&lt;/i&gt; leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model.Beta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in <i>WDR45</i>. 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 <i>WDR45</i>'s role in establishing and maintaining neurological function. Here we generated and characterized a mouse model bearing a c52C > T BPAN patient variant in <i>Wdr45.</i> We show this mutation ablates <i>WDR45</i> 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 ac2025-01-01T00:00:00Z20252025-04-20T00:09:30.582Z2025-04-20T00:09:30.582ZS-EPMC119076534009206510.3389/fnins.2025.1545004