Cover: Confocal immunostaining of the developing trachea and esophagus in E13.5 transgenic Foxg1Cre;mTmG embryos. Membrane-GFP lineage tracing (green) shows the recombined splanchnic mesenchyme; red indicates non-recombined cells; magenta is immunostaining of Acta2, indicating the developing smooth muscle; and blue is DAPI-stained nuclei. See article by Nasr et al. (dmm046573). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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Modeling the developmental origins of pediatric cancer to improve patient outcomes
Summary: This Perspective discusses the special features that make it challenging to develop new therapies for pediatric cancers, and the ways in which collaboration centered on improved models can meet these challenges.
Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies
Summary: Current animal models of bronchopulmonary dysplasia suffer from a lack of standardization, which hampers the translational relevancy of findings. Here the current state of available models is reviewed, offering recommendations for improvement.
AIRE deficiency, from preclinical models to human APECED disease
Summary: In this Review, we discuss the in vivo and in vitro models available to study AIRE deficiency, and how they may contribute to restoring immunological tolerance in APECED patients.
The infantile myofibromatosis NOTCH3 L1519P mutation leads to hyperactivated ligand-independent Notch signaling and increased PDGFRB expression
Summary: Analysis of the L1519P mutation in NOTCH3 and the relationship between Notch and PDGF signaling in infantile myofibromatosis revealed that NOTCH3L1519P generates hyperactivated, ligand-independent Notch signaling, which acts epistatically over PDGF signaling.
Altered cytoskeletal arrangement in induced pluripotent stem cells and motor neurons from patients with riboflavin transporter deficiency
Summary: This study deals with pathomechanisms underlying riboflavin transporter deficiency, a rare recessively inherited early-onset neurodegenerative condition. Using patient-derived iPSCs, we report on cytoskeletal abnormalities, which are reverted by combined riboflavin/antioxidant treatment.
Cardiovascular phenotype of the Dmdmdx rat – a suitable animal model for Duchenne muscular dystrophy
Summary: We characterized the cardiovascular abnormalities of Dmdmdx rats, demonstrating that Dmdmdx rats show similar cardiac and vascular endothelial function impairments to Duchenne muscular dystrophy patients, representing a model of the dystrophic heart.
Genetic background modifies vulnerability to glaucoma-related phenotypes in Lmx1b mutant mice
Summary: We observed that Lmx1b mutant mice of different strain backgrounds vary in onset and severity of glaucoma-related phenotypes and identified a modifier locus on Chr 18. These results could increase understanding of the mechanisms underlying glaucoma.
A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities
Editor’s choice: Brief exposure of the mouse testis to a muscle growth-promoting molecule initiates a cascade of molecular changes that expands over time, even when the treatment has stopped.
Inducible expression of human C9ORF72 36× G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice
Summary: Only 36 C9ORF72 repeats are sufficient for RAN translation in a new mouse model for amyotrophic lateral sclerosis and frontotemporal dementia. Reducing toxic dipeptides can prevent but not reverse the phenotype.
Hearing impairment due to Mir183/96/182 mutations suggests both loss-of-function and gain-of-function effects
Summary: Our study describes mice carrying knockout alleles of microRNAs involved in hearing and suggests that a point mutation in a microRNA can have a greater phenotypic impact than a null allele.
RET inhibition in novel patient-derived models of RET fusion- positive lung adenocarcinoma reveals a role for MYC upregulation
Summary: Establishment of four patient-derived models of RET fusion-positive lung adenocarcinomas with three different RET fusions shows that MYC expression is regulated by RET.
Neural crest-specific loss of Bmp7 leads to midfacial hypoplasia, nasal airway obstruction and disordered breathing, modeling obstructive sleep apnea
Summary: Using morphometric, respiratory function and metabolomics analyses, we demonstrate that the Bmp7 neural crest knockout mouse is a model for nasal airway obstruction with a craniofacial origin, allowing the study of disordered breathing.
TDP-43 mislocalization drives neurofilament changes in a novel model of TDP-43 proteinopathy
Summary: We examined the cellular effects of mislocalization of TDP-43, a key pathological protein in amyotrophic lateral sclerosis and frontotemporal dementia, using the eye as a model and demonstrated axonal cytoskeleton alterations.
Disruption of a Hedgehog-Foxf1-Rspo2 signaling axis leads to tracheomalacia and a loss of Sox9+ tracheal chondrocytes
Summary: Genetic and molecular analyses of mutant mouse embryos reveal a HH-Foxf1-Rspo2 signaling axis that informs the mechanistic basis of tracheomalacia in individuals with Hedgehog pathway mutations.
Mutant non-coding RNA resource in mouse embryonic stem cells
Summary: Analysis of a large library of mouse embryonic stem cell lines with gene trap insertions revealed mutations in 2202 unique non-coding RNA genes, which will significantly contribute to the functional annotation of non-coding RNA genes.
DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens
The abstract submission deadline for our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ is 14 July 2023. Find out more and register here.
The Forest of Biologists
The Forest of Biologists is a biodiversity initiative created by The Company of Biologists, with support from the Woodland Trust. For every Research and Review article published in Disease Models & Mechanisms a native tree is planted in a UK forest. In addition to this we are protecting and restoring ancient woodland and are dedicating these trees to our peer reviewers. Visit our virtual forest to learn more.
Propose a new Workshop for 2025
Do you have an idea for a Workshop? If so, click here. We are now accepting proposals for our 2025 Workshops programme. As the scientific organiser, your involvement will be focused on the science. We'll take care of all the logistics. In 2025 we'll continue our efforts to diversify our Workshop programme and will be reserving one of our Workshops for an application from a Global South country to host an event overseas.
How stromal cells restrict liver cancer invasion
In our recent editor’s choice, Liqin Zhu and colleagues describe how they used in vitro liver spheroid models consisting of both parenchymal and non-parenchymal cells to reveal a hepatoprotective role for peritumoral hepatic stellate cells in liver tumorigenesis.
And from perspective… Hacking haematopoiesis – emerging tools for examining variant effects
Thousands of genomic loci have been linked to hematopoietic traits and diseases, yet many await functional validation. Michael Gundry and Vijay G. Sankaran discuss recent advances in genome editing and the challenges associated with using these techniques to assess variant function in primary hematopoietic cells.