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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.

Conditional Gene Knockout Mouse

August 29, 2018
ingenious
Conditional Knockout

Conditional Gene Knockout Mouse

Conditional Gene Knockout Mouse

Conditional Gene Knockout Mouse Models and Their Invaluable Contribution to Genetic Research

The more we know about conditional gene knockout mouse models, the greater the chance that future researchers can use studies and tests done on these laboratory mice to discover invaluable breakthroughs in genetic research and medicine. As science progresses, systems based on basic mouse knockouts and the development of conditional gene inactivation through the Cre-lox system continue to progress significantly in their accuracy and in providing concrete, practical and usable results.

Selecting the Correct Mouse Models

Before a conditional gene knockout mouse can be developed, the correct mouse models have to be found and properly prepared for the process. While many types of mice can be used, the best are models that already have a null allele in their germline, and can be prepared to become mouse models of various diseases or to help researchers study gene targeting in ES cells, as well as in vitro gene function. While these mice typically have short lifespans, the Cre-lox recombination system can also be used to study their development as adult mice.

How the Conditional Gene Knockout Process Works

In order to develop a conditional gene knockout mouse, it’s necessary to understand how conditional gene knockouts really work. The process differs from methods that are used to obtain traditional gene knockouts, because conditional gene knockouts feature inactivations that occur at a certain, designated time. To overcome many of the problems that are associated with regular gene knockouts – such as random targeting or accidental embryonic death – researchers adopt technologies like Cre-lox. This allows them to target specific tissues, inactivate genes only in adulthood, or induce a change that allows them to study the development of impaired tissue over a longer period of time.

Conditional Gene Inactivation with the Cre-lox System

With the help of the Cre-lox system, obtaining conditional gene knockouts is relatively easy. The recombination essentially allows for the two strands of DNA to exchange information with each other. The result is a recombination between the two lox sites that can be obtained at a specific time with the help of chemicals like tamoxifen and tetracycline. These compounds have the role of activating the transcription of the Cre recombinase and initiating its transport to the nucleus. If researchers are able to find practical ways to express the Cre-recombinase in a living organism such as a mouse – which is typically the most difficult part of the experiment – there can be extremely valuable obtained results.

The Uses of Conditional Gene Knockouts

A conditional gene knockout mouse can be an important tool to genetic researchers. Many scientists use these mouse models to analyze and study the origination of diseases and genetic impairments that occur when certain genes are inactivated at specific times. This practice has allowed geneticists to study complex diseases like cancer and their development at a molecular level. The development of cancer cells can now be monitored at every stage of its progression. In addition, the new insights that practices such as the deletion of the BRCA1 allele in the mouse’s mammary gland tissue have already led to significant breakthroughs in tumor suppression. Conditional gene knockout mouse models are constantly being utilized to map the normal development of the body, as well as the progression of a number of genetic diseases that the Cre-lox system allows scientists to mimic quite faithfully.

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