This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Popular Press Review
Popular Press Review of “Progress is Reported on a Type of Autism” by Nicholas Wade.
The New York Times, February 20, 2007
This article highlights a study that has been able to reverse the symptoms of Rett Syndrome in mice by manipulating the MECP2 gene. Rett syndrome is on the autism spectrum and mainly effects girls. It is caused by a single gene, MECP2, which was discovered by Dr. Adrian Bird in 1990. Dr. Bird has been able to genetically engineer a strain of mice with MECP2 genes with an insertion that inactivated them, which caused mice to develop symptoms resembling Rett Syndrome. He also created a strain of mice with a gene that could remove the insertion in MECP2 when activated by tamoxifen. When mice with both genes were fed tamoxifen, they stopped expressing symptoms resembling Rett Syndrome. The author explains that these symptoms are reversible because MECP2 is not involved until neurons have already developed. MECP2 is responsible for silencing genes that are no longer needed. This research is important because it shows that Rett Syndrome could potentially be cured by correcting the mutated gene. But, this is a difficult task. MECP2 is located on the X chromosome and the father’s copy is damaged during spermatogenesis in Rett Syndrome. Females have two X chromosomes and one copy is inactivated in each cell throughout the body. A potential form of gene therapy would be to activate the X chromosome with the functional copy of MECP2 in girls with Rett Syndrome. Researchers are also considering determining the genes that MECP2 is responsible for silencing and creating drugs to repress them.
In this article, Wade does a good job explaining difficult science. His explanations MECP2’s gene silencing function and the role that X inactivation plays with Rett Syndrome were especially effective. The author also explained the importance of this research well with respect to Rett Syndrome specifically as well as the implications it can have for treating neurological diseases in general. Both of these aspects are important in a popular press article which is meant to convey science to the lay reader. The organization of this article could have been more effective. The author explains in the second and third paragraphs that the gene involved with Rett Syndrome would be corrected in mice but the treatment would not work in humans before explaining the function of the gene and the treatment method. I believe that this information would have been easier to understand after the background information was explained. To the lay reader, this may devalue the research. The author also describes Rett Syndrome as “a severe form of autism” in the first sentence of the article. This is oversimplified and inaccurate because some people with Rett Syndrome experience symptoms that resemble autism. This article shows the fine line between making information easy to understand for the lay reader and providing them enough information to be accurately informed.
Scentific Article Review
Scientific Article Review of “Reversal of Neurological Defects in a Mouse Model of Rett Syndrome”
Guy, J., Gan, J., Selfridge, J., Cobb, S., Bird, A. (2007) Reversal of Neurological Defects in a Mouse Model of Rett Syndrome. Science. 315 (23) pg. 1143-1147.
Rett syndrome is caused by mutations in the X-linked MeCP2 gene. Patients with Rett syndrome have abnormal neurons but the neurons do not die. Conditional deletions of MeCP2 in the neurons of mice showed that the mutant phenotype is specifically due to a lack of MeCP2 in neurons.
A mouse model was created where the endogenous MeCP2 gene was silenced by inserting a lox-Stop cassette. The silenced MeCP2 gene can be activated by deleting the cassette. A transgene expressing a Cre recombinase and an estrogen receptor (Cre-ER) fused with the MeCP2lox-Stop allele was created in order to control activation. Tamoxifen, an analog of estrogen, is used to cause the Cre-ER protein, which resides in the cytoplasm, to enter the nucleus and delete the cassette.
Though injections of Tamoxifen caused successful deletion of the cassette and activation of MeCP2, 9 out of 17 mice died due to toxicity of the injection. The other 8 mice survived and resembled wildtype mice. Thus, rapid activation of MeCP2 by injection of Tamoxifen may lead to either death or phenotypic rescue. When activation was induced more gradually, toxicity was eliminated.
Observational tests were used to monitor the phenotypes of wildtype mice, Stop/y mice male, and Stop/y male mice treated with Tamoxifen. Stop/y mice showed symptoms of Rett Syndrome where Stop/y mice treated with Tamoxifen initially showed symptoms of Rett Syndrome but they were reduced to being mild. The experimental mice treated with Tamoxifen also had longer lifespans.
However, Rett Syndrome is primarily seen in females because a mosaic of mutant and wildtype MeCP2 is expressed due to random X inactivation, which allows them to have a normal lifespan. Stop/+cre female mice with symptoms resembling Rett Syndrome were injected with Tamoxifen and their phenotypes reverted towards wildtype. Researchers were also able to show that a high percentage of neurons contained the MeCP2 protein after treatment with Tamoxifen, presumably due to recombination on the active X chromosome.
In addition, a study was conducted to determine the effect of MeCP2 on neuronal signaling. Electrophysiological analysis was used to determine Long-term potentiation (LTP), which is reduced in MeCP2 mutant mice, in the hippocampus of MeCP2 heterozygous females and wildtype controls. LTP levels after onset of Rett Syndrome symptoms were found to be reduced as compared to before symptoms occurred in MeCP2 heterozygous females. Researchers also found that LTP levels could be reversed to wildtype levels after treatment with Tamoxifen, which suggests that the neuronal signaling phenotype can be rescued in adult mice when active MeCP2 is reintroduced.
The authors propose that MeCP2 targets genes involved in neuron function through DNA methylation. This hypothesis would account for the ability of MeCP2 introduced in adult organisms to restore wildtype phenotypes.
This study suggests that symptoms that resemble Rett Syndrome in mice that lack MeCP2 can be reversed by gradual reintroduction of the active MeCP2 gene. This study was effective in testing this reversibility in both physical and neurological symptoms. I also found it effective that the researchers made sure to use MeCP2 heterozygous female mice as a model, since this the type of individual that Rett Syndrome affects in humans. The researchers used several controls and tested their theory on several levels. For example, they used western blots and in situ immunofluorescence to confirm that MeCP2 Stop/y mice did not produce MeCP2 protein. The only possible weakness in this paper is that they do not spend much time explaining their final hypothesis about MeCP2 targeting methylated genes. This is probably because their experiments didn't study this. I also thought it was important that the authors clearly stated that this research does not lead to a direct therapy but instead, it suggests that neurological disorders in humans may not be irreversible.
Popular Press vs. Scientific Article Critique
The two articles reviewed are notably different. The popular press article gives a very general summary of the results of the research and spends more time discussing the background of genetic concepts, such as X inactivation and gene silencing. Conversely, the scientific article goes into great detail on the research results and methods used and does not give much of an explanation of about background information.
This is because the two articles are written for different audiences and have different goals. The popular press article is meant to inform a very broad audience of the advancements in science. They are written for people who may not know much about science and require a “human element” that keeps the reader interested. Scientific articles are meant to be read by fellow scientists, who have extensive knowledge about basic genetic processes. It is also important for scientific articles to include as much detail as possible in order to accurately inform the scientific community.
As a member of the scientific community, I believe that popular press articles should include more in depth explanations of difficult science. The general public has very little knowledge and many misconceptions about scientific advancements in genetics and how they can affect individuals. Accurate information about new advancements in science is important for both individual health care and public policy decisions.
Jessica Connor
[email protected]
Last Updated: 3/3/09