Genetics INSIGHTS

Preventing Genetic Drift in Germ-Free Mice

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Maintaining genetic integrity within breeding colonies is always a critical issue, but this is especially the case for germ-free and gnotobiotic mice1. Due to the small size and closed nature of most gnotobiotic colonies, these lines are especially vulnerable to genetic drift via the accumulation of novel mutations2,3. In the worst-case scenario, this might lead to the unintentional fixation of mutations in inbred strains, with potentially devastating...  Read More

Reference DNA from Key Mouse Strains Now Available

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Reproducibility Requires Genetic Quality The genetic integrity of laboratory mice and rats is an important contributor to research reproducibility, which is why commercial animal vendors invest in maintaining the genetic quality of standard inbred and outbred strains. As the technology to produce genetically engineered models (GEMs) becomes more widespread, a growing majority of GEMs are bred and used at individual institutions. This decentralization has created concerns regarding...  Read More

Genetic Variation in C57BL/6 ES Cells and Knockout Mice

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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...  Read More

Cystic Fibrosis Treatment from Vertex May Restore Lung Function

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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...  Read More

Oh Transgene, Where Art Thou?
Mapping Transgene Insertion

photo from Oh Transgene, where Art Thou?<br> 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...  Read More

Variations within Outbred Strains: Know Your Strains and Stocks

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The Sprague Dawley® (SD) rat is one of the most popular outbred stocks, with application across many therapeutic areas as well as ADMET studies. The SD is an outbred stock, meaning that there is genetic variation within the stock, and each individual varies in genetic makeup. Genetic variation is maintained through well-defined rotational mating schemes, which are designed to maintain heterozygosity within the population over time. The...  Read More

Improving Lives by Modeling Rare Genetic Disorders

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Relief for patients with rare genetic disorders are often out of reach, due to the expense of developing genetically engineered animal models. That's why the Rare Genomics Institute, Taconic Biosciences, and Jonah's Just Begun came together to develop and characterize a model of Sanfilippo Syndrome. Sanfilippo Syndrome is a progressive, devastating rare genetic disorder affecting approximately 1 in 70,000 children. There are four subtypes of the disease,...  Read More

Congenic Mice: What's in a Name?

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Researchers unfamiliar with mouse genetics can be confused by complex strain nomenclature, leaving them unsure how to select controls for a particular test strain. The nomenclature of congenic mice records a wealth of useful information, including both donor and recipient strains and mutations of interest. One common example of this is confusion around background strain for GEM and mutant lines. While it is common now to make...  Read More

Using CRISPR to change "A" to "T" and "C" to "G"

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The use of this acronym has become ubiquitous in the life sciences. For those who don't know, CRISPR stands for Clustered Regularly Interspersed Palindromic Repeats. We hear people talking about it in the context of gene editing of cell lines and animal models. There are now scientific conferences devoted to CRISPR technology, CRISPR in the clinic and CRISPR engineering of animal models. While the intellectual property landscape...  Read More