Issues
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Cover image
Cover Image
Cover: Aggregates of dVAPB(P58S), in red, are visualized in the Drosophila third instar larval brain using an antibody generated against the coiled-coil domain of the protein. The mutant protein is expressed in neurons using the UAS-Gal4 system. The aggregates/puncta mimic inclusions seen in human ALS patients with the hVAP(P56S) mutation. The authors find that ROS levels modulate aggregates by triggering their clearance through the ubiquitin proteasomal system. ROS, in the context of their experiments, is in turn regulated by SOD1 activity and also by the strength of mTOR signaling. This study uncovers gene networks in neurons that regulate aggregate dynamics. See article by Chaplot et al. (dmm033803). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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EDITORIALS
A thank you to DMM's peer reviewers
Summary: DMM highlights changes in our peer-review process, and thanks peer reviewers for their involvement in this vital step in scholarly publication.
From gene to treatment: supporting rare disease translational research through model systems
Summary: This Editorial discusses the importance of model systems with accurate face, construct, target and predictive validity for rare disease research.
FIRST PERSON
SPECIAL ARTICLE
The Human Cell Atlas: making ‘cell space’ for disease
Summary: In this Special Article, the author reflects on the potential of the Human Cell Atlas project for improving our understanding of disease.
REVIEW
Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models
Summary: Investigation of the crosstalk between the Wnt and other signaling pathways will improve understanding of orofacial cleft development and provide opportunities for treatment and prevention.
RESEARCH ARTICLES
Differential regulation of the unfolded protein response in outbred deer mice and susceptibility to metabolic disease
Summary: By using genetically diverse deer mice, we show that the expression of different chaperones is highly coordinated in individual animals and its profile predicts the onset of metabolic pathology.
Leptin induces muscle wasting in a zebrafish kras-driven hepatocellular carcinoma (HCC) model
Summary: Through a zebrafish model, this study demonstrates that leptin plays an important role in cancer-induced muscle wasting and that the leptin pathway may be a therapeutic target in cancer cachexia.
VPS13A is closely associated with mitochondria and is required for efficient lysosomal degradation
Summary: VPS13A, which is implicated in chorea-acanthocytosis, is essential for efficient lysosomal degradation, while localized in close association with mitochondria. We propose that inter-organelle communication may be relevant in the pathogenesis of the disease.
Loss of Frrs1l disrupts synaptic AMPA receptor function, and results in neurodevelopmental, motor, cognitive and electrographical abnormalities
Summary: Loss of the epilepsy-related gene Frrs1l in mice causes a dramatic reduction in AMPA receptor levels at the synapse, eliciting severe motor and coordination disabilities, hyperactivity and cognitive defects, with some evidence of behavioural seizures.
Serotonin inhibits axonal regeneration of identifiable descending neurons after a complete spinal cord injury in lampreys
Summary: Pharmacological and genetic manipulations show that endogenous serotonin inhibits axonal regeneration of individually identifiable descending neurons of lampreys after a complete spinal cord injury.
ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic Caenorhabditis elegans
Summary: We report new humanized nematode models of amyloid-beta and apolipoprotein E gene expression, examining readouts for neurodegeneration, behavior, cellular function and survival, to elucidate the relative contributions of the proteins to the underlying pathology of Alzheimer's disease.
Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating free DNA
Summary: A liquid biopsy approach is capable of tracking early lung cancer lesions, before the adenoma-adenocarcinoma transition, in an early lung cancer mouse model driven by a KRAS mutation.
A double-hit pre-eclampsia model results in sex-specific growth restriction patterns
Summary: Double-hit exposure to the anti-angiogenic factor soluble fms-like tyrosine kinase and the pro-inflammatory endotoxin lipopolysaccharide in mice provides a novel, comprehensive model of pre-eclampsia, which leads to sex-specific metabolomic differences in fetuses.
SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in a Drosophila model of amyotrophic lateral sclerosis
Summary: ALS8/VAPB(P58S) aggregates appear to be cleared by an increase in cellular reactive oxygen species, which, in turn, triggers proteasomal degradation.
Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity
Summary: Adeno-associated-virus-mediated gene therapy for insulin receptor isoform A expression in the liver improves glucose disposal and alleviates lipid accumulation in wild-type mice under a high-fat diet.
A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects
Editor's choice: Mitochondria are conserved among eukaryotes and mutations in the factors that control their dynamics are causal for various human disorders. Hence, yeast models can be used for pharmacological screenings.
PREPRINT HIGHLIGHTS
New Special Issue: Translating Multiscale Research in Rare Disease. Edited by Monica Justice, Monkol Lek, Karen Liu and Kate Rauen.
![](https://cob.silverchair-cdn.com/ImageLibrary/DiseaseModelsMech/Snippets/dmm17_6_cover.jpg?versionId=7319)
This special issue features original Research, Resources & Methods and Review-type articles that aim to interrogate the mechanisms of rare diseases to foster meaningful clinical progress in their diagnosis and treatment.
The role of the International Society for Stem Cell Research (ISSCR) guidelines in disease modelling
![Vital role of the International Society for Stem Cell Research (ISSCR) in promoting the efficient translation of basic research.](https://cob.silverchair-cdn.com/ImageLibrary/DiseaseModelsMech/Snippets/faksignalling_600x416.png?versionId=7319)
The ISSCR provides comprehensive guidelines and standards for using human stem cells in biomedical research. In this Editorial, Cody Juguilon and Joseph Wu discuss how and why these should be incorporated in disease modelling research.
Subject collection: Building advocacy into research
![Colourful visual showing two individuals with speech bubbles filled with icons incl money, medicine, stethoscope and a microscope](https://cob.silverchair-cdn.com/ImageLibrary/DiseaseModelsMech/Snippets/0224_DMM_collection_advocacy_v2.png?versionId=7319)
DMM’s series - Building advocacy into research - features interviews, ‘The Patient’s Voice’, with patients and advocates for a range of disease types, with the aim of supporting the highest quality research for the benefit of all patients affected by disease.
Read & Publish Open Access publishing: what authors say
![Promotional banner for R&P agreements](https://cob.silverchair-cdn.com/ImageLibrary/DiseaseModelsMech/Snippets/1023_DMM_RP_whatauthorssay.jpg?versionId=7319)
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
Biologists @ 100 - join us in Liverpool in March 2025
![Biologists @ 100 - Register now - 24-27 March 2025](https://cob.silverchair-cdn.com/ImageLibrary/Development/Snippets/Snippet%20image_600x230_RGB_RegisterNowv2.png?versionId=7319)
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.