GEMs DESIGN INSIGHTS


Genetic Variation in C57BL/6 ES Cells and Knockout Mice

Genetically engineered animal models (GEMs) are powerful tools for biomedical research and drug discovery, but genetic variation in animal models derived from distinct ES cell lines and subsequent breeding can impact both the interpretation and reproducibility of studies which employ them1. While recent advances in gene editing accelerated the migration of models to a pure C57BL/6 background, researchers should remain aware of potentially confounding results from genetic...

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Cystic Fibrosis Treatment from Vertex May Restore Lung Function

Cystic Fibrosis (CF) is a genetic disorder that affects the lungs, digestive system, and a host of metabolic functions. In humans, CF is a progressive disease, where chronic dysfunction of muco-ciliary clearance leads to severe congestion, thick mucus build-up, and severe persistent lung infections. In 1960 the median life expectancy for a patient with CF was ten years old. However, with significant advances in research and clinical...

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Oh Transgene, Where Art Thou?
Mapping Transgene Insertion

Over the last three decades, transgenic mice have become a critical in vivo modeling tool in biomedical research. Transgenic technique1, whereby an exogenous gene is inserted into the mouse genome by direct injection of DNA into the pronuclei of a zygote, has enabled thousands of new transgenic lines to be created2. However the technique is not without limitations. One of the biggest drawbacks of using pronuclear injection...

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New Vici Syndrome Mouse Model Could Accelerate Research

Most rare diseases have a genetic component, making access to an animal model with the associated gene mutation a must for developing new therapies. Yet these diseases don't often attract the funding to develop a genetically engineered model of the condition. With the help of Taconic Biosciences, two investigators studying Vici syndrome now have this essential research tool in hand. Vici syndrome is a severe congenital multisystem...

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CRISPR Genome Engineering: Advantages and Limitations

Four years after the debut of CRISPR/Cas9 in mouse genetics, it is time to start drawing some conclusions on its performance, advantages, and limitations as a genome engineering technology1,2,3. Advantages of CRISPR Genome Engineering Arguably, the most important advantages of CRISPR/Cas9 over other genome editing technologies is its simplicity and efficiency. Since it can be applied directly in embryo, CRISPR/Cas9 reduces the time required to modify target...

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Why Your Transgenic Project Failed

Erroneous modification of the mouse genome can lead to the generation of transgenic lines carrying non-functional alleles or unwanted mutations. These faulty models can seriously impact your research program, wasting resources on misleading results. Are Design Errors Driving Translational Failure? Genetically modified mouse models first appeared more than thirty years ago and are still at the heart of biomedical research. The first models carried relatively simple genetic...

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Genetically Engineered Models in Drug Development

Why do 90% of compounds fail the FDA approval process after entering Phase I clinical trials?1 Many failed projects can be traced to unreliable preclinical assessments of toxicity and efficacy of the potential new drugs2 – often due to a lack of predictive and reliable in vivo testing. Wild-type mice and rats were the gold standard in the assessment of efficacy and toxicity for many years, due...

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Key Immunology Mouse Models in History

While the field of immunology has origins that date back to the 1500s, the field gained significant ground with the expanded use of mouse model systems. Fundamental discoveries elucidated in mouse models over the past 50 years are beginning to yield major breakthrough treatments for the most sinister human diseases, including inflammatory bowel disease, neurodegeneration, and cancer. The immunologist's major professional association, the American Association of Immunology,...

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Versatile Applications of the TNFα Mouse

Research models are often engineered to help answer a narrow set of experimental questions; however, cross-breedings and other experimental interventions allow investigators to dramatically broaden the utility of transgenic mouse models. This is particularly true for models with strong and relatively easy-to-monitor phenotypes, two properties which support a potential platform for multiple rapid discoveries. One such example is the human TNFα mouse: a transgenic mouse that over-expresses...

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Targeting APOE4 for Alzheimer's Disease Therapies

Past research efforts, focused on Alzheimer's disease (AD) pathology and the genetics of familial AD, led to the discovery of important AD-related proteins, including amyloid-beta (Aβ) and tau. However, efforts to develop AD therapies based on targeting Aβ and tau have largely failed. Years of disappointing trials have brought increasing demand for new AD targets and alternative treatment approaches. Using mice expressing apolipoprotein E4 (apoE4), a human...

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