FGFR3
is part of a complicated network that is required for normal bone growth and
development. Achondroplasia-associated mutation increases the negative role of
FGFR3 (anti-proliferative), causing growth inhibition. Although FGFR3 appears
to have an anti-proliferative role in bones, it has been shown to promote
proliferation in other tissues. So, what makes FGFR3 function differently in
different tissues, and why is it important for us to understand this? To be
able to identify and test molecular targets for drug, we have to find
out how does Ach-associated FGFR3 mutation cause increased growth inhibition in
bones. We need the sequence of events downstream of FGFR3 signaling that are
negatively affected by this mutation. By comparing proliferative vs inhibitory
role of FGFR3, we might get some indication of what is happening in bones due
to the mutations. All of this requires dissecting out the molecular details of
FGFR3 signaling and regulation. Although the initial experiments need to be
carried out in cultured cells, they will need to be eventually tested
in live animals - genetically engineered mice in our case. Our plan is to
use such mice (transgenic mice) models to understand the role of
FGFR3 signaling in bone growth. First, it will be useful to understand what are
transgenic mice and how are they generated.
Transgenic mice models are frequently used in the study of human diseases due to their genetic similarities with humans. They are easy to manipulate and work with. Most importantly, they provide a method to study the effect of a single gene or protein without disturbing any other factors in the animal. In simple terms, transgenic mice expressing the mutant form of a disease-related gene would mimic the conditions associated with the human disease, and thus allow us to observe and study the effect of that mutation in the system.
Generation of transgenic mice involves several steps. Foreign genetic material - the transgene - is incorporated into the genome of a mouse to generate transgenic mice. There are several methods available for the method of delivery of the transgene and efficient incorporation of the transgene into the genome. Following link (2 part video) provides an overview of how transgenic system works. http://www.youtube.com/watch?v=ujZHrR1mro8
Transgenic mice models are frequently used in the study of human diseases due to their genetic similarities with humans. They are easy to manipulate and work with. Most importantly, they provide a method to study the effect of a single gene or protein without disturbing any other factors in the animal. In simple terms, transgenic mice expressing the mutant form of a disease-related gene would mimic the conditions associated with the human disease, and thus allow us to observe and study the effect of that mutation in the system.
Generation of transgenic mice involves several steps. Foreign genetic material - the transgene - is incorporated into the genome of a mouse to generate transgenic mice. There are several methods available for the method of delivery of the transgene and efficient incorporation of the transgene into the genome. Following link (2 part video) provides an overview of how transgenic system works. http://www.youtube.com/watch?v=ujZHrR1mro8
Also,
for further reading:
1. Van Keuren ML et
al. “Generating transgenic mice from bacterial artificial chromosomes:
transgenesis efficiency, integration and expression outcomes.” Transgenic Res.
2009 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016422/?tool=pubmed)
2.
Connelly CS et al. “The role of transgenic animals in the analysis of various
biological aspects of normal and pathologic states.” Exp Cell Res. 1989. (http://www.ncbi.nlm.nih.gov/pubmed/2670592)
No comments:
Post a Comment