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.
Limitations:
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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