Reduced body weight is a common effect of gene knockout in mice

<p>Abstract</p> <p>Background</p> <p>During a search for obesity candidate genes in a small region of the mouse genome, we noticed that many genes when knocked out influence body weight. To determine whether this was a general feature of gene knockout or a chance occurrence, we surveyed the Jackson Laboratory Mouse Genome Database for knockout mouse strains and their phenotypes. Body weights were not available for all strains so we also obtained body weight information by contacting a random sample of investigators responsible for a knockout strain.</p> <p>Results</p> <p>We classified each knockout mouse strain as (1) lighter and smaller, (2) larger and heavier, or (3) the same weight, relative to control mice. We excluded knockout strains that died early in life, even though this type of lethality is often associated with a small embryo or reduced body size. Based on a dataset of 1,977 knockout strains, we found that that 31% of viable knockout mouse strains weighed less and an additional 3% weighed more than did controls.</p> <p>Conclusion</p> <p>Body weight is potentially a latent variable in about a third of experiments that use knockout mice and should be considered in interpreting experimental outcomes, e.g., in studies of hypertension, drug and hormone metabolism, organ development, cell proliferation and apoptosis, digestion, heart rate, or atherosclerosis. If we assume that the knockout genes we surveyed are representative then upward of 6,000 genes are predicted to influence the size of a mouse. Body weight is highly heritable, and numerous quantitative trait loci have been mapped in mice, but "multigenic" is an insufficient term for the thousands of loci that could contribute to this complex trait.</p

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Request for Community partnership in data resource licensing planning

<p>We write an open letter to the NIH Data Research Council to initiate a dialog regarding NIH decisions on data use agreements and licenses. We are members of NIH-funded research groups that collect and/or integrate biomedical data from diverse sources for the purpose of advancing diagnosis, prognosis, treatment selection, and mechanistic discovery. </p><p><br></p><p>We welcome additional signatories here:</p><p>https://docs.google.com/document/d/1fbwKxnPu5f1YXlMM6UMyfBqHx_Inz86tKzwRFO4W8jQ<br></p><br><p>Summary:</p><br><ul><li><p>The current diversity of data use agreements and licenses significantly hampers the ability to reuse and redistribute data in various informatics contexts.</p></li><li><p>We believe that any mandatory data licensing policy must also include a plan for ensuring access, sustainability, and data quality. </p></li><li><p>We request community partnership with NIH to develop common licensing and data reuse plans. </p></li></ul