Issues

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.

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.

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.

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.

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.

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.

Summary: A single peripheral dose of a recombinant natural human IgM increases lifespan and delays neurological deficits in mouse models of human ALS.

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.

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.

Summary: This work underscores the importance of studying cancer metastasis using in vivo model systems in addition to in vitro and transplant model systems.

Summary: The authors identified proteins involved in Wnt/β-catenin-driven alveolar epithelial plasticity in lung injury and repair.

Summary: In the fission yeast S. pombe, kidney disease-associated mutations in Myo1, a homolog of human Myo1e, disrupt myosin localization and function.

Summary: The comparison of different nephron-specific Wt1-knockout mouse models identifies the stage of origin of human WT1-mutant Wilms' tumours.

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.

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.

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.

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.

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.

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.

Highlighted Article: Apoc2 loss-of-function zebrafish display severe hypertriglyceridemia, which is characteristic of human patients with defective lipoprotein lipase activity.

Summary: Phospholamban overexpression in mouse slow-twitch muscle impairs SERCA function and causes histopathological features associated with human centronuclear myopathy.