With a $50,000 grant from FRAXA Research Foundation from 2002-2004, Dr. Edouard Khandjian and his team at Laval University studied the functions of FMR1 and the related genes FXR1 and FXR2 in frogs.
Laeticia Davidovich, PhD
FRAXA Postdoctoral Fellow
Project Plan
by Edouard Khandjian, 1/1/2002
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 simpler. Progress has been made identifying genes which are regulated by FMRP, FXR1P, and FXR2P using microarray analysis; some of these may be targets for potential drug development.
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.
