I am proud to share our work on X-linked Dystonia-Parkinsonism — a rare neurodegenerative movement disorder driven by a SINE-VNTR-Alu retrotransposon insertion in the TAF1 gene. Read our two companion papers: 🔹 www.biorxiv.org/content/10.1... 🔹 www.biorxiv.org/content/10.1... 🧵 Highlights below!

What do you do when there’s no model for a rare disease? YOU BUILD ONE!

Together with @kerrylimberg.bsky.social, @liddelowsa.bsky.social, @jefboeke.bsky.social, & many amazing collaborators, we show that inducing the humanized XDP-TAF1 allele in neural progenitor cells recapitulates key features of the human disease 👉 striatal atrophy and progressive motor decline.

🐭 The motor deficits are wild! Check it out!

But here’s the twist… 🧠 Contrary to the long-standing view of XDP being a medium spiny neuron-specific disorder, we discovered oligodendrocyte dysfunction and widespread myelin disruption as a major and previously unrecognized hallmark of disease pathology — in both mice and human patient brains.

These findings expand the view beyond neurons, revealing glial contributions to XDP and the broader role of retrotransposons in shaping brain health and disease. 🧠 Read the whole story: 'Myelin pathology is a key feature of X-linked Dystonia Parkinsonism' www.biorxiv.org/content/10.1...

🧬 Dive into the complex genetics of the XDP mice in our companion paper led by Weimin Zhang, Yu (Jeremy) Zhao, Ran Brosh, Jef Boeke, and team: 'Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism' www.biorxiv.org/content/10.1...

This work represents a close collaboration between the @liddelowsa.bsky.social 🫶 @jefboeke.bsky.social labs at NYU Grossman School of Medicine as a part of The Dark Matter Project @darkmatterproject.bsky.social.

This work was primarily funded by the Collaborative Center for XDP (CCXDP) and NHGRI’s Center of Excellence in Genomic Science – The Center for Synthetic Regulatory Genomics at NYU Langone Health.