TAF1

UNderstanding X‐linked dystonia Parkinsonism

X‐linked Dystonia Parkinsonism (XDP), a rare inherited form of Parkinsonism endemic to the Philippines with an average onset age of 40 is caused by an SVA retrotransposon insertion in the TAF1 gene. SVA is a primate-specific composite retrotransposon present in about 1000 copies in the human genome and constitutes an Alu‐like sequence, a portion of an endogenous retrovirus, a VNTR (variable number of tandem repeats) sequence and a hexameric tandem repeat (CCCTCT)n. Longer repeats are associated with lower age of onset of XDP.

TAF1 is the largest subunit of the multisubunit Transcription factor II D (TFIID), which recognizes the TATA box and is required for initiation of transcription by RNA polymerase II.

Our goal is to generate mouse models of X‐linked Dystonia Parkinsonism by engineering a chimeric mouse/human TAF1 gene, including the XDP-causing SVA insertion and variants of it that differ in the number of (CCCTCT)n repeat units. These unique mice will express a mouse Taf1 protein from a gene that has the same structure as the human TAF1 and will be a valuable tool to the XDP research community.

IN COLLABORATION WITH:

Shane A. Liddelow, PhD, NYU Langone Health

Priya Prakash, PhD, NYU Langone Health