Tuesday, January 14, 2014

Knock Out Mouse (KO Mouse)

Knock Out mouse is a genetically modified mouse in which a particular gene is removed or inactivated. As a particular gene (which encodes for a particular protein) is inactivated, the mouse shows changes in external features or physical and biochemical characteristics. The first recorded knock out mice was produced in 1989 for which Martin Evans and Oliver Smithies were awarded Nobel Prize.

The various reasons for producing knock out mice are

·        To understand the function of a gene
·        To understand various diseases which are due to alterations or mutations in genes
·        It gives an idea for understanding and treating various diseases
·        To develop and test various drugs produced

Some of the diseases which are widely studied using mouse models are neuronal diseases like Parkinson’s disease, Alzheimer’s disease and various types of cancer are also understood with the help of KO mouse models. Besides these, KO mice are also used for studying heart diseases, diabetes, obesity etc.

For producing knock out mouse, a DNA fragment is designed such that it contains some random sequence in place of the gene to be knocked out with flanking sequences similar to that of the sequences which are flanking the particular gene (to be knocked out) in the original genome. Moreover, the DNA fragment also contains markers to detect the effect of knock out or Embryonic stem (ES) cells are generally used for knock out, the ES cells are collected and transfected with the DNA fragment designed. Homologous recombination occurs resulting in knock out and the cells which are knocked out are transferred back into the blastocyst, then the blastocyst is placed in the uterus of a surrogate mother (mouse) which gives birth to knock out mice.

Why knock out “mouse”?

The next question that comes into our mind is “why mouse? Why not other species?”
The reasons for using mouse as a model for understanding human diseases and genes are the similarity between the genome of mouse and humans to a greater extent. And also mouse is easy to handle.

There are also limitations in producing knock out mouse. Most of the knock outs are lethal so the knocked out mouse cannot grow up and survive for a longer period. It is difficult to produce a knock out mouse as there are always possibilities for random or non homologous recombination. Producing knock out rat is difficult, and the first knock out rat was produced in 2003, 14 years after the production of KO mouse.

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