IN THIS ISSUE
EDITORIAL
- Embracing risk
Summary: We are entering an era of unprecedented promise for solving some of humankind's most pressing health issues. In this Editorial, Ross Cagan emphasizes the importance of taking risks in science and in career choices.
REVIEW
- RASopathies: unraveling mechanisms with animal models
Summary: Developmental disorders caused by germline mutations in the Ras-MAPK pathway are called RASopathies. Studies with animal models, including mice, zebrafish and Drosophila, continue to enhance our understanding of these diseases.
RESEARCH ARTICLES
- A state of reversible compensated ventricular dysfunction precedes pathological remodelling in response to cardiomyocyte-specific activity of angiotensin II type-1 receptor in mice
Highlighted Article: A novel conditional mouse model was used to investigate early initiating stages of heart disease that are commonly overlooked, and identifies a ‘window of opportunity’ for personalised therapeutic intervention.
- Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways
Summary: Tomoregulin-1 is primarily involved in embryonic development and adult CNS function. To the authors' knowledge, this is the first study about the function of tomoregulin-1 on cardiac hypertrophy in mice.
- Glycoprotein A33 deficiency: a new mouse model of impaired intestinal epithelial barrier function and inflammatory disease
Highlighted Article: We show that GPA33, an intestine-specific cell surface protein, plays a role in the maintenance of intestinal barrier function and the prevention of intestinal pathologies such as food hypersensitivity, inflammatory bowel disease and colitis-associated cancer.
- Optineurin deficiency in mice contributes to impaired cytokine secretion and neutrophil recruitment in bacteria-driven colitis
Summary: Optineurin plays a role in acute inflammation, proinflammatory cytokine secretion and neutrophil recruitment, which suggests that diminished optineurin expression in humans might increase the risk of developing Crohn's disease.
- A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosis
Summary: A single peripheral dose of a recombinant natural human IgM increases lifespan and delays neurological deficits in mouse models of human ALS.
- A Drosophila model for mito-nuclear diseases generated by an incompatible interaction between tRNA and tRNA synthetase
Summary: Interacting mutations in a mitochondrially encoded tRNA and nuclear-encoded tRNA synthetase result in a suite of pathologies, including altered locomotor capacity, mitochondrial function and morphology, and mitochondrial translation.
- Using the avian mutant talpid2 as a disease model for understanding the oral-facial phenotypes of oral-facial-digital syndrome
Summary: This study utilizes a naturally occurring avian mutant known as talpid2 to determine the cellular basis for the oral-facial phenotypes present in oral-facial-digital syndrome.
- MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma
Summary: This work underscores the importance of studying cancer metastasis using in vivo model systems in addition to in vitro and transplant model systems.
- Enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells
Summary: The authors identified proteins involved in Wnt/β-catenin-driven alveolar epithelial plasticity in lung injury and repair.
- Effects of FSGS-associated mutations on the stability and function of myosin-1 in fission yeast
Summary: In the fission yeast S. pombe, kidney disease-associated mutations in Myo1, a homolog of human Myo1e, disrupt myosin localization and function.
- Deducing the stage of origin of Wilms' tumours from a developmental series of Wt1-mutant mice
Summary: The comparison of different nephron-specific Wt1-knockout mouse models identifies the stage of origin of human WT1-mutant Wilms' tumours.
- Targeting tubulointerstitial remodeling in proteinuric nephropathy in rats
Summary: Targeting lymphangiogenesis, inflammation or fibrosis separately in a rat model of proteinuric nephropathy showed that treating any of these changes alone is not effective in treating the disease.
- Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice
Summary: GSK3 promotes renal fibrosis by activation of TGF-β signaling, and the use of GSK3 inhibitors might represent a novel therapeutic approach for progressive renal fibrosis that develops as a consequence of acute kidney injury.
- Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome
Summary: In vivo analysis of zebrafish esco2 mutants reveals extensive genomic instability and activation of DNA-damage-response pathways, although some cells have compensatory cohesion and divide normally.
- Sun1 deficiency leads to cerebellar ataxia in mice
Summary: Mice lacking Sun proteins serve as a working model to study SYNE1-associated cerebellar ataxia; they will also be useful in identifying therapeutic targets for neurodegenerative diseases involving Purkinje cell loss.
- Phenotypic and functional characterization of Bst+/− mouse retina
Summary: We characterized Bst+/− mice and found that pupillary light reflex was completely absent, which could be used as a readout for the efficacy of stem cell therapy in this model.
- Ethambutol induces impaired autophagic flux and apoptosis in the rat retina
Summary: This study provides the first evidence that EMB induces autophagosome accumulation, which results from the impaired autophagic flux that is mediated by a PKCδ-dependent pathway, and leads to apoptotic death in retina neuronal cells.
RESOURCE ARTICLES
- Apoc2 loss-of-function zebrafish mutant as a genetic model of hyperlipidemia
Highlighted Article: Apoc2 loss-of-function zebrafish display severe hypertriglyceridemia, which is characteristic of human patients with defective lipoprotein lipase activity.
- Phospholamban overexpression in mice causes a centronuclear myopathy-like phenotype
Summary: Phospholamban overexpression in mouse slow-twitch muscle impairs SERCA function and causes histopathological features associated with human centronuclear myopathy.
This issue
Other journals from The Company of Biologists
DMM and COVID-19
We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.
Please don’t hesitate to contact the Editorial Office if you have any questions or concerns.
A Model for Life – Elizabeth McNally and Louis Kunkel
Human geneticist and cardiologist Elizabeth McNally discusses her first experiences in science and the effort we all need to make to facilitate diversity in science, while Louis Kunkel tells us about talks about his discovery of dystrophin.
On the cover of our special issue, Demonbreun et al. present muscle fiber typing from a newly created mouse model of limb-girdle muscular dystrophy generated by gene editing.
Non-canonical autophagy in innate immune defence in vivo
preLighter Kirsty Hooper, The Babraham Institute, Cambridge, UK, discusses a preprint showing that loss of non-canonical autophagy in mice increases sensitivity to influenza A virus infection.
The Biology Open transfer option
DMM authors can transfer their submission to our sister journal Biology Open with just one click. An online Open Access journal, BiO also welcomes direct submissions and focuses on the swift publication of high-quality, sound research. Recent disease modelling highlights in BiO include work by Liu et al. investigating transgenic replenishment strategies targeting myocardial and non-myocardial tissues in the zebrafish. Find out more about how to transfer.
Editor’s choice
Highlighted by the Guest editors of our special issue, Grunwald and colleagues use zebrafish to investigate interactions among ryanodine receptor isotypes in muscle development and function, while Claire Wood et al. tests the mdx:Cmah−/− mouse to investigate growth and skeletal development in Duchenne muscular dystrophy.