Issues
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Cover image
Cover Image
Cover: Immunohistochemical staining of an embryonic day (E)18.5 Exoc5 conditional knockout mouse ureter with E-cadherin (green), smooth muscle actin (red) and DAPI (blue) reveals complete rescue of in utero ureteropelvic junction obstruction with a single treatment of the broad-spectrum caspase inhibitor z-VAD-FMK at E16.5. See article by Ortega et al. (dmm049785). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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EDITOR'S CHOICE
EDITORIAL
Sharing resources to advance translational research
Summary: Disease Models & Mechanisms announces the launch of a new Outstanding Resource Paper Prize. To mark the occasion, we highlight exciting recent Resource articles and discuss their importance for biomedical research.
PERSPECTIVE
Animals, quality and the pursuit of relevance
Summary: Lack of reproducibility in animal studies continues to be a challenge, and improving this is a National Institutes of Health priority. Key strategies to enhance translatability are offered and discussed by The Jackson Laboratory investigators.
REVIEWS
The Finnish genetic heritage in 2022 – from diagnosis to translational research
Summary: This Review discusses the unique enrichment of variants causing Finnish disease heritage disorders and the discovery of novel genotype–phenotype associations underlying monogenic and common complex diseases.
Defining the unknowns for cell therapies in Parkinson's disease
Summary: Cell therapies for Parkinson's disease have entered into first-in-human clinical trials. Here, we discuss pertinent outstanding questions that require consideration before widespread adoption of this therapeutic intervention and remain to be further explored.
Molecular inhibition of RAS signalling to target ageing and age-related health
Summary: This Review critically discusses the links between RAS signalling and ageing, and how RAS inhibitors could extend lifespan and enhance healthspan.
RESEARCH ARTICLES
Integrated multi-omics analysis of Huntington disease identifies pathways that modulate protein aggregation
Summary: Metabolomic analysis of Huntington disease (HD) patients and of a HD yeast model identified deregulated metabolic pathways. We used the yeast model to investigate their role in the aggregation of huntingtin protein and their implications in HD.
Abnormalities in the migration of neural precursor cells in familial bipolar disorder
Summary: Cell migration patterns are abnormal in neural precursors derived from bipolar disorder patients, which could contribute to the already known structural changes in the brain.
Lipopolysaccharide distinctively alters human microglia transcriptomes to resemble microglia from Alzheimer's disease mouse models
Summary: Using single-cell RNA sequencing to measure the induced pluripotent stem cell-derived microglia response, we find convergence between ATPγS and lipopolysaccharide (LPS)+IFN-γ; however, comparison to genetic mouse models indicates LPS as a better model for Alzheimer's disease.
Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling
Summary: Targeted Exoc5 deletion in embryonic ureter urothelial progenitor cells impairs autophagy, causing Fn14 activation and urothelial cell death, with a lethal congenital obstructive uropathy rescuable by administration of a caspase inhibitor.
A clinically relevant model of acute respiratory distress syndrome in human-size swine
Summary: A pre-clinical model of acute respiratory distress syndrome (ARDS) in human-sized swine, which recapitulates the clinical, radiographic and histopathologic manifestations of ARDS, providing a tool to study therapies for this highly morbid lung disease.
Targeting firing rate neuronal homeostasis can prevent seizures
Editor's choice: Epilepsy remains challenging to treat. In this study, we show that manipulating endogenous mechanisms that maintain stability of neuronal activity represents a possible route to better manage this disorder.
Stimulating the sir2–spargel axis rescues exercise capacity and mitochondrial respiration in a Drosophila model of Barth syndrome
Summary: Nicotinamide riboside rescues the exercise capacity and mitochondrial function of a Drosophila model of Barth syndrome in a Sir2/Spargel-dependent manner.
RESOURCE ARTICLE
An adherent-invasive Escherichia coli-colonized mouse model to evaluate microbiota-targeting strategies in Crohn's disease
Summary: Adherent-invasive Escherichia coli (AIEC)-colonized transgenic mouse ‘Vill-hCC6’ reproducing ileal colonization by AIEC observed in Crohn's disease is proposed as a new tool to evaluate AIEC-targeting strategies.
FIRST PERSON
PREPRINT HIGHLIGHTS
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.