Edouard Khandjian, PhD, Principal Investigator
Laeticia Davidovich, PhD,
Postdoctoral Fellow
Laval University, Quebec, Canada
$35,000 in July 2004
$24,000 in 2002
This group is studying the functions of
FMR1 and the related genes FXR1 and FXR2 in frogs.
While frogs have the same number of genes (3) in this
family of genes, they have far fewer isoforms of the
protein products compared to humans (where FMRP
alone can exist in at least 12 distinct forms), making study
of the different functions somewhat simpler. Progress has
been made in this project identifying genes which are
regulated by FMRP, FXR1P, and FXR2P using microarray
analysis; funding is being continued in hopes of identifying
new targets for potential drug development.
by Edouard Khandjian, January 2002
Animal models have been generated to study the normal functions of the FMRP protein, which is lacking in fragile X syndrome. These animal models are either extremely complex---such as mouse, or very primitive---such as fish, worm and fly. Mammals have two other genes, FXR1 and FXR2, which are closely related to the Fragile X gene. Altogether, these three genes code for many different forms of proteins that have a complex pattern of expression in different tissues and organs. It is thought that the two related proteins FXR1P and FXR2P can partially compensate for the absence of FMRP, but this hypothesis needs further testing. In the more primitive fly model, these three different genes are all replaced by a single gene (dFXR), so differential tissue expression studies are not possible.
We began to study an animal model that is genetically closer to man than to flies. This animal, the frog Xenopus laevis, contains all three genes, but the number of protein forms coded by these genes is much smaller than in mammals, which allows us to study protein expression in a simpler environment. The frog model is an extraordinarily flexible experimental tool since it is possible to directly address questions about the functions of each protein, either during development or in the adult animal. This can be done by introducing different molecules into the egg through micro-injection, before or after fertilization, in order to induce a phenotype. Once this model has been developed, new avenues to study the functions of the FXR proteins in the nervous system will hopefully be unveiled.
