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"I’ve been working with iTL over the past 5 years in the production of 3 different genetically altered mice. Not only did iTL help in the design of the mice, […]” - Raghu Mirmira, MD, PhD University of Chicago.
BAC transgenic mice are an invaluable tool for preclinical research as demonstrated by decades of use across many human disease areas. Understanding the potential of these mouse models can help you choose the right one for your next research project. So let’s take a closer look at exactly what BACs are, how they’re used to create animal models, and a few examples of where these models are used.
BACs (bacterial artificial chromosomes) are DNA molecules with specific properties that make them useful in a number of ways. They were originally developed to address a specific problem encountered by researchers trying to understand how genes function. Scientists wanted to study genetic sequences of 100,000 base pairs or more but they couldn’t easily manipulate DNA molecules that large. A BAC can contain a genetic sequence of up to 300,000 base pairs and the development of this technology opened up multiple new research possibilities.
Mouse models are widely used around the world to study genetically inherited diseases, with the goals of understanding, treating, and one day curing them. Animal research can be a vital part of a project to understand a human condition and BACs can be used to create a specific, valuable type of animal model: the BAC transgenic. A BAC can contain the entire sequence of a human gene, such as one that’s associated with a particular genetic disease. This gene sequence can be permanently integrated into the genetic makeup of a mouse. Using these transgenic mice makes it possible to observe how the gene functions in vivo, and potentially understand its relationship with a genetic disease.
However, the use of BACs to generate transgenic mice is still accompanied by several problems. BAC transgenes are generated by nonspecific integration into the target genome; therefore a variable number of copies can be inserted into an unknown locus in the genome of the target organism. Also, the generation of BAC transgenic founders is less efficient than conventional transgenes; it usually results in less founder lines being generated in the course of a similar microinjection effort. These issues can be potentially avoided by generating targeted transgenic mice, through either a cDNA knockin to your gene of interest or a safe-harbor transgenic knockin.
Bacterial artificial chromosomes can contain genetic sequences that are known to be associated with conditions such as neurological disorders. For example, a scientific study may identify a gene mutation that could make people more prone to seizures. A BAC containing the mutated gene sequence could be used to successfully generate a BAC transgenic mouse. Researchers have used BAC animal models to better understand seizure disorders in humans, with the goal of developing new treatments for these conditions.
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