Summary: This Editorial discusses advances in modelling neuromuscular disorders to improve the translatability of preclinical studies. It also highlights two articles from this issue of DMM that provide a deeper understanding of X-linked myotubular myopathy.
A MODEL FOR LIFE
Summary: This Review discusses the available in vitro models to investigate the impact of adhesion of Plasmodium falciparum-infected red blood cells on the blood–brain barrier, a process associated with cerebral malaria.
Summary: Pyroptosis is a form of inflammatory cell death. Here, we compare the interplay between pyroptosis and important human pathogens, i.e. Mycobacterium tuberculosis, Salmonella Typhimurium and Shigella flexneri, across different models of immune response to infection.
Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
Summary: Validation of an inducible model of myotonic dystrophy type 1 that shows altered cellular stress responses. These involve phase-separated cellular structures also implicated in other degenerative conditions.
Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A
Summary: The hepatic-gut neural axis plays a role in NAFLD progression via serotonin and the serotonin receptor HTR2A in hepatocytes, suggesting that HTR2A antagonists are potential therapeutic agents for NAFLD.
Bisphenol-A impairs synaptic formation and function by RGS4-mediated regulation of BDNF signaling in the cerebral cortex
Summary: Bisphenol-A (BPA) disrupts normal synaptic transmission and cognitive behavior in mice. Rgs4 transcription factor and its downstream BDNF/NTRK2 pathway appear to mediate the effect of BPA on synaptic and neurological function.
Arap1 loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death
Summary: We provide evidence that Arap1 expression in retinal pigment epithelium (RPE) is essential for maintaining photoreceptor health due to its indispensable role in RPE phagocytosis.
Natural history study and statistical modeling of disease progression in a preclinical model of myotubular myopathy
Summary: This study optimized disease severity analysis and modeled disease progression in Mtm1−/y mice, and confirmed this model using therapeutic Dnm2 reduction in a dose–response analysis.
Contribution of model organism phenotypes to the computational identification of human disease genes
Editor's choice: We investigated the use of model organism phenotypes in the computational identification of disease genes, identifying several data biases and concluding that mouse model phenotypes contribute most to computational disease gene identification.
Summary: This study provides a comprehensive and longitudinal molecular and phenotypic evaluation of the disease process of X-linked myotubular myopathy (XLMTM) in a murine model.