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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.
Genetic research has come a long way in the past few years alone as a result of advancements made with the help of conventional knockout animal models. The knockout process is designed to inactivate a gene in an organism with the help of an artificial piece of DNA used to replace or disable the gene in question. Conventional knockouts are of interest to the scientific community because of the role they play in determining the numerous unknown details of why a certain gene behaves as it does. Also, they tell us why gene function might be impaired by certain factors and what can be done to restore it to its natural, healthy behavior.
Mouse models are at the forefront of a large percentage of the studies dedicated to understanding DNA sequences and specific, individual genes with the help of conventional knockout procedures. This fact isn’t solely true because mice are genetically similar to humans – since other mammals, such as chimps and apes share an even greater similarity with us in terms of their genetic makeup – but also because mice are small in size, and the specific procedures that make knockout techniques work can be more easily applied to mice than to any other laboratory animal. As opposed to mice, even gene knockout in rats has been extremely difficult to apply, and has only been possible for the past 15 years.
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Unlike conditional mouse models, in which genes are inactivated in a specific location or tissue, a conventional knockout is much broader in scope. These knockouts involve disabling a gene throughout the entire organism, which is why their outcomes can be harder to predict and to control. Knocking out a gene in the entire body, however, can shed crucial light on what the role of that gene is in each and every area of the organism. With its help, researchers can have a much broader and more detailed view of how the knockout gene influences even some of the most subtle processes in the body and how its inactivation can contribute to or impair the development of various diseases.
While more advanced procedures such as conditional knockouts and conventional knockouts in rats have not been around as long, conventional knockout mice have been used long enough for scientists to develop thousands of useful strains. To make nomenclature easier to keep track of, most mouse models are named after the gene that’s been knocked out. Strains are developed after careful evaluation of the types of genes that are most important to explore – such as genes responsible for encoding proteins that have tumor-suppressant properties. Such strains have effectively helped scientists learn about the subtler processes of what causes tumors to form and how they can be countered.
Advancements in genetic technology are being made every year. The latest technologies, like CRISPR and advanced transgenic procedures are considered the cutting edge today, when it comes to greatly diminishing the limitations of using conventional knockouts for genetic research and the development of genetic therapies. When it comes to the details of a conventional knockout and its function, scientists hope to gradually use these techniques and their future versions to prevent embryo fatality and develop better, more accurate humanized mouse models to account for instances when the genetic differences between mice and human DNA are too great.
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