Institute for Frontier Life and Medical Sciences, Kyoto University

Facioscapulohumeral muscular dystrophy: Visualization of a primate-specific DUX4-expressing lineage in mice

Date: July. 30, 2019 14:00~15:30
Room: Seminar Room No.3, 1st Floor, Bldg. #1 of Institute for Frontier Life and Medical Sciences, Kyoto University
Speaker: Dr. Yosuke Hiramuki
Department of Pharmacology,
Center for Molecular Medicine,
University of Nevada, Reno
Title: (Japanese) Facioscapulohumeral muscular dystrophy: Visualization of a primate-specific DUX4-expressing lineage in mice

<Abstract>

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disorder that initially affects specific muscles of the face, shoulder girdle, and upper arms in an asymmetric manner. The causative gene is double homeobox 4 (DUX4), which is specific to primates. DUX4 is normally only expressed in germ cells and repressed in somatic cells. Loss of repression leading to aberrant low frequency expression in skeletal muscles causes FSHD. However, it remains unclear how DUX4 expression is controlled in adult tissues and during development in FSHD patients. Here, we generated transgenic mice that express Cre under the control of the human DUX4 regulatory regions. When crossed with R26NZG reporter mice, which express LacZ under the control of the CAG promoter in response to Cre expression, we sought to follow DUX4-expressing lineage by X-gal staining. Among adult tissues, testicular germ cells were consistently stained at high frequency, while other tissues including skeletal muscle showed variable staining patterns, and regenerating myofibers with central nuclei after muscle injury were stained at very low frequency. During embryogenesis, the face at E14.5 had a particular staining pattern that overlapped with the skeletal muscle alpha-actin gene expression. These X- gal staining patterns in mice and either human DUX4 expression or FSHD phenotype have some similarities, indicating that further analyses with these novel transgenic mice could give insight into understanding the molecular mechanisms regulating DUX4 expression in FSHD pathology.

(Language: Japanese)