Emerging preclinical animal models for FSHD

Angela Lek; Fedik Rahimov; Peter L Jones; Louis M Kunkel

doi:10.1016/j.molmed.2015.02.011

Emerging preclinical animal models for FSHD

Trends Mol Med. 2015 May;21(5):295-306. doi: 10.1016/j.molmed.2015.02.011. Epub 2015 Mar 20.

Authors

Angela Lek¹, Fedik Rahimov², Peter L Jones³, Louis M Kunkel²

Affiliations

¹ Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Children's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; The Wellstone Program, Departments of Neurology and Cell and Developmental Biology, University of Massachusetts Medical School (UMMS), Worcester, MA 01655, USA. Electronic address: alek@enders.tch.harvard.edu.
² Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Children's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; The Wellstone Program, Departments of Neurology and Cell and Developmental Biology, University of Massachusetts Medical School (UMMS), Worcester, MA 01655, USA.
³ The Wellstone Program, Departments of Neurology and Cell and Developmental Biology, University of Massachusetts Medical School (UMMS), Worcester, MA 01655, USA; The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIHCD) Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Massachusetts Medical School, Worcester, MA, USA.

Abstract

Facioscapulohumeral dystrophy (FSHD) is a unique and complex genetic disease that is not entirely solved. Recent advances in the field have led to a consensus genetic premise for the disorder, enabling researchers to now pursue the design of preclinical models. In this review we explore all available FSHD models (DUX4-dependent and -independent) for their utility in therapeutic discovery and potential to yield novel disease insights. Owing to the complex nature of FSHD, there is currently no single model that accurately recapitulates the genetic and pathophysiological spectrum of the disorder. Existing models emphasize only specific aspects of the disease, highlighting the need for more collaborative research and novel paradigms to advance the translational research space of FSHD.

Keywords: DUX4; facioscapulohumeral dystrophy; muscular dystrophy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Homeodomain Proteins / genetics
Humans
Models, Animal
Muscular Dystrophy, Facioscapulohumeral / genetics*
Muscular Dystrophy, Facioscapulohumeral / pathology*

Substances

Homeodomain Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding