Issues
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Cover image
Cover Image
Cover: Representative image showing reduced intraepidermal nerve fibre density in the footpads of mice fed a high-fat diet as histological evidence of small sensory nerve fibre loss. UCHL1 (also known as PGP9.5)-positive fibres are shown in green; DAPI-stained nuclei are shown in blue. See article by Eid and Feldman (dmm049337). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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EDITOR'S CHOICE
EDITORIAL
A MODEL FOR LIFE
PERSPECTIVES
Insulin at 100 years – is rebalancing its action key to fighting obesity-related disease?
Summary: Insulin resistance drives obesity-related diseases, but it is a complex state featuring loss and gain of insulin action, and dysregulated crosstalk with growth factor signalling. ‘Rebalancing’ signalling may offer a beneficial addition to current therapy.
Advances in diet-induced rodent models of metabolically acquired peripheral neuropathy
Summary: Diet-induced models of peripheral neuropathy highlight the importance of diet composition, duration and source, with mouse strain, age and sex, in recapitulating human disease. Improved models will accelerate translation to the clinic and drug development.
RESEARCH ARTICLES
Reduction of oxidative stress suppresses poly-GR-mediated toxicity in zebrafish embryos
Summary: Toxicity of C9ALS/FTD poly-GR in zebrafish embryos is suppressed by Trolox, and poly-GR can be detected and quantified in zebrafish model protein homogenates, and in the frontal cortex of C9FTD/ALS cases.
Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans
Summary: A tool for quantitative image analysis of muscle deterioration that allows predicting healthspan in the nematode model Caenorhabditis elegans and may lead to the first C. elegans-based high-throughput sarcopenia screening platform.
TP53 loss initiates chromosomal instability in fallopian tube epithelial cells
Summary: High-grade serous ovarian cancer is defined by TP53 mutation and chromosomal instability (CIN), the cause of which remains poorly understood. We developed a novel model system that implicates cell cycle deregulation upon p53 loss as cause of CIN.
Cell death-inducing cytotoxicity in truncated KCNQ4 variants associated with DFNA2 hearing loss
Summary: Expression of truncated KCNQ4 variants lacking the C-terminal tetramerization domain results in cell-death inducing cytotoxicity, providing novel insight into the development of alternative therapeutic strategies for DFNA2 hearing loss.
Early manifestations and differential gene expression associated with photoreceptor degeneration in Prom1-deficient retina
Summary: The early manifestations of an inherited retinal disease was investigated by means of a transcriptome analysis, and a possible drug-based therapeutic approach (endothelin receptor antagonists) is suggested.
Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Editor's choice: We report the unexpected finding that systemic administration of diphtheria toxin induces rapid regression of murine lung adenocarcinomas expressing human EGFRL858R in the absence of a transgenic allele containing human diphtheria toxin receptor.
Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability
Summary: Genetic STAT3 ablation in mice and VEGF-inducible zebrafish reveals that VEGF signals through STAT3 to promote vascular permeability. Pyrimethamine reduces VEGF-induced permeability in animal models.
Novel zebrafish polycystic kidney disease models reveal functions of the Hippo pathway in renal cystogenesis
Summary: A zebrafish stk3 mutant line and Wwtr1 overexpression line provide evidence for functions of the Hippo signaling pathway in renal cyst formation and represent potential models for polycystic kidney disease.
RESOURCE ARTICLE
A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow
Summary: We report the first mouse model of isolated hypoplastic left heart syndrome (HLHS), allowing for the investigation of abnormal cardiac, brain and placental development that is implicated in HLHS.
FIRST PERSON
DMM Journal Meeting 2024: Pre-clinical Modelling of Human Genetic Disease and Therapy

Registration is open for our 2024 Journal Meeting. Rapid advances in gene editing and genetic technologies have revolutionised our ability to model human genetic disease and provided new hope for gene therapies. At this Meeting, speakers will present the very latest advances in modelling human genetic disease.
Moving towards heart success – Disease Models & Mechanisms Special Issue

DMM's most recent special issue compiles articles that investigate the genetic and biological mechanisms of heart failure and identify potential therapeutic strategies.
Sustainable Conferencing Initiative

Through our Sustainable Conferencing Grants, we promote the use of new technology and greener modes of travel. Our blog posts showcase examples of sustainability in action and share guidance about how new technologies and different conference formats work in practice.