This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison
Future Directions
As with any mental disease, with a Fragile X genotype there can be a range of phenotypes, ranging from slightly autistic to mildly through severely mentally disabled. One area I propose as an area of future research to shed light on this vast range of phenotypic differences would be the protein-protein interactions of a functional FMR1 protein and possible phenotypes of null mutants of each protein in the mouse model organism. The hope would be that by identifying other proteins with null functions in more severely disabled FXS children and adults that their phenotypes could be caught sooner and their families could be given appropriate counseling and each FXS patient’s learning regime could correspond to any particular difficulties they face.
My proposed hypothesis would be that knock-outs (KO) of FMRP binding proteins or even the FMR1 homologs, FXR1 and FXR2, would create FXS similar phenotypes in the mouse model.
My proposed hypothesis would be that knock-outs (KO) of FMRP binding proteins or even the FMR1 homologs, FXR1 and FXR2, would create FXS similar phenotypes in the mouse model.
FMRP immunostain in mice hippocampus
FXS mice characteristically have audiogenic seizures, a seizure which is inducible with loud noises. This is not surprising, as some cases FXS patients also can have seizures, although I do not believe they are inducible with loud noises. Other than showing the mice have FXS similar audiogenic seizures it would be important to show localization of the different proteins in both wild-type (WT) mice brains and the knock-out (KO) brains. To the left you can see a sliver of both WT and FMR1 KO hippocampal regions of the respective mice brains. These brains were immunostained for the FMR1 protein, which means that a stain has attached to the protein showing where it is localized in the hippocampus. As you can see the WT mouse has much more FMRP present and localized in the hippocampus, whereas the FMR1 KO mouse has noticeably less protein localized in the same region.
Ideally each FMR1 interacting protein would show similar expression patterns in both the WT and KO immunostaining and have other phenotypic expression of FXS-like states characterized in mice.
The importance of identifying other key proteins that might rescue severity of some full mutation Fragile X patients could be crucial to better understanding a disease that is born at a frequency 1/4000 [2].
Ideally each FMR1 interacting protein would show similar expression patterns in both the WT and KO immunostaining and have other phenotypic expression of FXS-like states characterized in mice.
The importance of identifying other key proteins that might rescue severity of some full mutation Fragile X patients could be crucial to better understanding a disease that is born at a frequency 1/4000 [2].
References
[1]Zeier, Z., Kumar, A. et al. (2009) Fragile X mental retardation protein replacement restores hippocampal synaptic function in a mouse model of fragile X syndrome. Gene Therapy. 1122-1129
[2] The National Fragile X Foundation: h ttp://www.nfxf.org/html/genetic_counselor.htm
[2] The National Fragile X Foundation: h ttp://www.nfxf.org/html/genetic_counselor.htm
Aime Agather
[email protected]
Last Updated 11/08/2010
Genetics 677
[email protected]
Last Updated 11/08/2010
Genetics 677