Progress Update: In vivo model to validate drugs targeting DUX4 enhancer/promoter activity

Posted by Friends of FSH Research on Oct 24, 2019

Progress update by Yosuke Hiramuki

Aberrant DUX4 expression in skeletal muscle leads to FSHD. Inhibiting DUX4 expression is a viable therapeutic approach for FSHD. Although several drugs that decrease DUX4 expression in a cell culture have already been identified, it is still unclear if these drugs will have the similar effect in a whole living organism. Considering mice do not have the DUX4 gene, in order to validate these drugs in mice, we need to generate genetically modified mice. In this study, we are using our novel mouse model, which contains the human FSHD region of chromosome 4q35 including the DNA sequences that regulate DUX4 expression, to genetically mark and trace cells in which DUX4 is expressed during muscle development. We are documenting when and where DUX4 is expressed during embryonic development, in adult tissues, and after stimulating muscle regeneration to determine whether these mice have a similarity to the limited known patterns of DUX4 expression in human. In addition, we will evaluate the effect of drugs targeting DUX4 expression in vivo.

See grant In vivo model to validate drugs targeting DUX4 enhancer/promoter activity