PUBLICATION
The effect of muscle glycogen phosphorylase (Pygm) knockdown on zebrafish morphology
- Authors
- Migocka-Patrzałek, M., Lewicka, A., Elias, M., Daczewska, M.
- ID
- ZDB-PUB-191121-12
- Date
- 2019
- Source
- The international journal of biochemistry & cell biology 118: 105658 (Journal)
- Registered Authors
- Keywords
- McArdle diseases, Muscle, Muscle form of glycogen phosphorylase, Pygm, Zebrafish
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Gene Knockdown Techniques
- Glycogen/genetics*
- Glycogen/metabolism
- Glycogen Phosphorylase, Muscle Form/genetics*
- Glycogen Storage Disease Type V/genetics*
- Glycogen Storage Disease Type V/metabolism
- Glycogen Storage Disease Type V/pathology
- Humans
- Muscle, Skeletal/metabolism*
- Muscle, Skeletal/pathology
- Mutation/genetics
- RNA, Messenger/genetics
- Zebrafish/genetics
- PubMed
- 31747538 Full text @ Int. J. Biochem. Cell Biol.
Citation
Migocka-Patrzałek, M., Lewicka, A., Elias, M., Daczewska, M. (2019) The effect of muscle glycogen phosphorylase (Pygm) knockdown on zebrafish morphology. The international journal of biochemistry & cell biology. 118:105658.
Abstract
Muscle glycogen phosphorylase (PYGM) is a key enzyme in the first step of glycogenolysis. Mutation in the PYGM gene leads to autosomal recessive McArdle disease. Patients suffer from exercise intolerance with premature fatigue, muscle cramps and myalgia due to lack of available glucose in muscles. So far, no efficient treatment has been found. The zebrafish has many experimental advantages, and was successfully implemented as an animal model of human myopathies. Since zebrafish skeletal muscles share high similarity with human skeletal muscles, it is our animal of choice to investigate the impact of Pygm knockdown on skeletal muscle tissue. The two forms of the zebrafish enzyme, Pygma and Pygmb, share more than 80% amino acid sequence identity with human PYGM. We show that the Pygm level varies at both the mRNA and protein level in distinct stages of zebrafish development, which is correlated with glycogen level. The Pygm distribution in muscles varies from dispersed to highly organized at 72 hpf. The pygma and pygmb morpholino knockdown resulted in a reduced Pygm level in zebrafish morphants, which exhibited altered, disintegrated muscle structure and accumulation of glycogen granules in the subsarcolemmal region. Thus, lowering the Pygm level in zebrafish larvae leads to an elevated glycogen level and to morphological muscle changes mimicking the symptoms of human McArdle disease. The zebrafish model of this human disease might contribute to further understanding of its molecular mechanisms and to the development of appropriate treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping