Obtaining the Perfect Gene Knockout – Mice and Their Role in Genetics
When using the right technology and methods to obtain a gene knockout, mice are found to be the best tool we can utilize. Mice are easy to work with, their lifespans allow for convenient long term experimentation, and their genome is close enough to the human genome to allow for humanized mice (mice with human DNA) to be developed. Knockout mice are the forefront of our genetic progress, and they have already played a major role in the discovery of countless effective treatments for diseases previously believed to be incurable.
Understanding Gene Knockouts
In a gene knockout, mice are genetically altered to live with one or more of their genes either altered by another snippet of DNA, or entirely disrupted. When done properly, a knockout mouse model can be an invaluable tool in studying the secrets and functions of the DNA and applying these findings to the human genome. Questions relating to human physiology and diseases affecting humans can then be answered more thoroughly, and without the need for any studies performed with human participants.
Why Are Mice Used in Knockouts?
When it comes to gene knockout, mice are believed to be the best candidates of all complex mammals. The first knockout mouse dates back to 1989, when it was developed by Mario R. Capecchi, Oliver Smithies and Martin Evans. Mouse models can help researchers learn more about the human condition due to the similarities between mouse and human genes. The areas of heart disease, diabetes, arthritis and substance abuse are just a few of the best examples where knockout mice have been remarkably helpful in obtaining new cures and treatments.
Procedures for Obtaining a Knockout Mouse
In terms of the process of obtaining a gene knockout, mice are easy to use. However, the process is still quite lengthy and complicated. It first involves isolating a gene in the mouse gene library and engineering a DNA sequence similar to the original gene, which will later be inserted into embryonic stem cells derived from a mouse blastocyst. After growing the cells in vitro, and introducing the new genetic sequence, the ES cells are then introduced into a new blastocyst which is implanted into the uterus of a healthy female mouse.
How Many Strains of Knockout Mice Are There?
When it comes to gene knockout, there are many mice that were designed to be models of various diseases or meant to test different types of drugs. Mouse strains exist in the thousands, and can be differentiated primarily based on the gene that was knocked out. They are named after the gene in question, and can be used for a variety of mutations and genetic manipulation techniques. Some mouse strains inhibit the function of genes that are responsible for halting cell growth, leading to a greater risk of the development of cancer cells. Others are specifically designed to impair gene function that is known as the source of various genetically inherited diseases. Several thousands of mouse strains are currently being used and studied worldwide, and that number is constantly growing.
Limitations of Knockout Mice
No practice is unlimited and perfect, even if it’s the most advanced of genetic modification procedures. When it comes to gene knockouts, the use of mice is primarily limited because there is a high mortality among gene knockouts (up to 15%). There are cases when the altered embryo cannot properly develop to adulthood, so the results of the experiment become meaningless. Moreover, it can be difficult to attest to the validity of certain results with regards to human genetics. The mouse genome still carries certain differences from the human one, so even with a successful gene knockout, mice aren’t always able to tell us whether or not certain treatments might be effective against the disease they are meant to treat.