Transgenic mouse model of Parkinsonism-dystonia type 2 (PKDYS2)

Genomic medicine provides potential for novel diagnostic targets and therapeutic solutions. As mutations in human genes are identified and associated with neurodevelopmental disorders, the need to create personalized treatment protocol has increased. We have previously reported the first mutation in type 2 vesicular monoamine transporter (VMAT2), causing an infantile Parkinsonism phenotype Parkinsonism-dystonia-2 (PKDYS2) (OMIM 618049)( Rilstone et al., NEJM, 2013). Over the past decade, several additional mutations have been identified in VMAT2, giving rise to a broad phenotype spectrum and variable responses to treatment (Saida et al 2023)(Zhai et al 2023). In the study of neurodevelopmental diseases, transgenic animal models offer an opportunity to investigate mutant genesand their role in pathophysiology, opening avenues for the advancements of therapeutic strategies to combat these conditions. Here, we delineated the first viable transgenic mouse model for the disease and analyzed the molecular impact of VMAT2 mutations. Furthermore, we are finalizing the behavioral characterization of this animal model. All combined, we are gaining an understanding of pathophysiology and developing personalized treatment protocols that would aid in guiding clinical decisions and enhancing patient outcomes for this, and possibly other, neurodevelopmental disorders affecting neurotransmission.