Zebrafish Models of LAMA2-Related Congenital Muscular Dystrophy (MDC1A).

Lacramioara Fabian,James J Dowling

doi:10.3389/fnmol.2020.00122

Abstract

LAMA2-related congenital muscular dystrophy (CMD; LAMA2-MD), also referred to as merosin deficient CMD (MDC1A), is a severe neonatal onset muscle disease caused by recessive mutations in the LAMA2 gene. LAMA2 encodes laminin α2, a subunit of the extracellular matrix (ECM) oligomer laminin 211. There are currently no treatments for MDC1A, and there is an incomplete understanding of disease pathogenesis. Zebrafish, due to their high degree of genetic conservation with humans, large clutch sizes, rapid development, and optical clarity, have emerged as an excellent model system for studying rare Mendelian diseases. They are particularly suitable as a model for muscular dystrophy because they contain at least one orthologue to all major human MD genes, have muscle that is similar to human muscle in structure and function, and manifest obvious and easily measured MD related phenotypes. In this review article, we present the existing zebrafish models of MDC1A, and discuss their contribution to the understanding of MDC1A pathomechanisms and therapy development.

Highlights

LAMA2-related congenital muscular dystrophy (CMD; LAMA2-MD), called merosin deficient CMD or MDC1A, is the most common subtype of CMD (Schorling et al, 2017; Sframeli et al, 2017; Mohassel et al, 2018; Mercuri et al, 2019)
MDC1A is an autosomal recessive neuromuscular disorder caused by mutations in laminin α2 (LAMA2, HelblingLeclerc et al, 1995; Holmberg and Durbeej, 2013)
Zebrafish Models of LAMA2 Disease that is associated with a later onset, milder form of muscular dystrophy (Nguyen et al, 2019)

Summary

Introduction

LAMA2-related congenital muscular dystrophy (CMD; LAMA2-MD), called merosin deficient CMD or MDC1A, is the most common subtype of CMD (Schorling et al, 2017; Sframeli et al, 2017; Mohassel et al, 2018; Mercuri et al, 2019). Mutations in zebrafish lama2 results in a type of muscular dystrophy phenotypically similar to the human MDC1A (Hall et al, 2007), which identifies zebrafish as a suitable model for understanding this disease and for development of therapies.

Results

Conclusion