Issues

Summary: With the co-publication of three research articles describing CRISPR/Cas9-based approaches for knocking in mutations in zebrafish (dmm035352, dmm035469 and dmm035972), this Editorial reflects on the current state of genome editing for disease modeling in zebrafish.

Summary: In this Review and accompanying poster, we discuss the dual role of the immune system in metastasis and summarize promising therapeutic strategies to target tumor-immune interactions.

Summary: The utility of mice as models of human disease is often questioned because they live in a controlled laboratory environment, unlike humans. The authors compare the environments of humans and mice, and find parallels, suggesting that they are not so different. Understanding how mouse and human environments affect phenotypes is critical for the development of models of human disease.

Summary: The homeobox genes Six4 and Six5 are involved in the regulation of cell proliferation and mesothelium formation in the primary body wall, and Six4^−/−;Six5^−/− mice are a suitable animal model for human middle-type omphalocele.

Summary: Here, we show that a minipig model of Huntington's disease mimics human neurodegeneration and holds promise for future intervention studies. However, minipig peripheral blood mononuclear cells express no detectable mutant huntingtin, eliminating their use as monitoring tools.

Summary: Zebrafish can be used to examine diabetic complications, including vision loss. Here, in zebrafish, we show that prolonged (4 week) hyperglycemia causes an inflammatory response associated with functional deficits localized to specific cone types.

Summary: The endothelial Nos3 mutation impacts neural-crest and second-heart-field lineage patterning within the aortic valve, which affects outflow-tract formation, as well as aortopulmonary angulation.

Summary: This study uses genome editing in zebrafish to demonstrate that a human DNA sequence variant of unknown significance might contribute to the complex genetics of congenital heart defects.

Summary: By using a single-stranded DNA oligonucleotide template in combination with CRISPR/Cas9 in zebrafish, the authors achieved effective germline-transmissible introduction of patient-specific single-nucleotide changes related to cardiovascular disease.

Summary: NGS-based analysis reveals that CRISPR/Cas9-induced double-strand-break repair using single-stranded repair templates is error prone in zebrafish, resulting in complex patterns of integrated repair-template fragments.

Summary: p21 inhibition in response to 17-DMAG treatment induces chondrogenesis in human synovial mesenchymal stem cells and promotes auricular cartilage regeneration in vivo.

Summary: Double knockout of Apoe and Ldlr on the highly atherosclerosis-resistant NOD mouse background results in severe atherosclerosis, which paves the way for the study of severe atherosclerosis in the setting of autoimmunity.

Summary: ENPP1 enzyme replacement therapy can have important implications for generalized arterial calcification of infancy by treating both vascular calcification and hypertension, which are the leading causes of cardiac failure and mortality in patients.

Editor's choice: ApoE knockout pigs displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries within 6 months of feeding on a high-fat and high-cholesterol diet.