C57BL/6JCya-Pygm^em1flox/Cya

Pygm, the muscle glycogen phosphorylase gene, encodes myophosphoylase, a key enzyme in the first step of glycogenolysis, the breakdown of glycogen to release glucose-1-phosphate. This process is crucial for muscle metabolism. Genetic models, such as the zebrafish and mouse models, are valuable for studying Pygm [2,4].

Mutations in Pygm lead to autosomal-recessive McArdle disease. In McArdle disease cellular models, read-through agents like amlexanox, Ataluren, RTC13, and G418 were evaluated for their ability to overcome the Pygm p.R50X mutation, but no detectable read-through was found [1]. In zebrafish, knockdown of Pygm led to an elevated glycogen level and morphological muscle changes similar to human McArdle disease symptoms, suggesting its role in muscle structure and glycogen regulation [4]. In AD, the expression of Pygm was decreased, and its down-regulation in neurons impaired synaptic plasticity and cognition in WT mice, while overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice, indicating its role in synaptic function and energy generation in neurons [3].

In conclusion, Pygm is essential for muscle glycogen breakdown and metabolism, with its dysfunction leading to McArdle disease. Studies in animal models also reveal its role in synaptic function in the context of AD. Understanding Pygm's functions through these models provides insights into the molecular mechanisms of these diseases, potentially guiding future treatment development.