Rett Syndrome Research Trust Website

by Monica Coenraads

It would be difficult to overestimate the importance of what we have learned from the mouse models of Rett Syndrome.  After all, without them we would not know that Rett is reversible.

It may come as a surprise that there is no single mouse model of Rett but rather a variety of genetic models, from “KO” or “knock-out” mice, which have no MeCP2 at all, to those in which the precise MeCP2 mutations that are seen in humans suffering from Rett Syndrome have been duplicated.

Jackson Laboratories in Bar Harbor, Maine currently distributes almost a dozen mouse models of Rett. Jackson (or Jax, as most scientists refer to it) is a non-profit organization that specializes in this work to advance the understanding of human disease. Although no animal model perfectly capitulates human symptoms or responses, 95% of our genomic information exists also in rodents. Maintaining an extraordinary level of care and attention to detail in this sensitive field, Jax conducts its own research as well as breeding and managing colonies of thousands of models.

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To learn more about Jax please read an earlier blog post, Of Mice and Men…Or in the Case of Rett…Of Mice and Women.

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Having access to the various models of Rett Syndrome is crucial to the advancement of research and this is an area that RSRT and its predecessor, RSRF, have been actively involved in since the first animal models were published in 2001 by RSRT Trustee and advisor, Adrian Bird and by Rudolf Jaenisch.

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From the Jax website:  “Partners in the fight against Rett syndrome,” a story about how Monica Coenraads, the mother of a daughter with Rett syndrome and co-founder of two organizations focused on treating it, is working with Dr. Cathy Lutz to develop and distribute new mouse models of Rett syndrome.

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Sharing mouse models is not always the norm as this article about a mouse model for Angelman Syndrome illustrates. We are extremely fortunate that researchers in the Rett field have been stellar about quickly sharing their models. Adrian Bird, Rudolf Jaenisch and Huda Zoghbi have set an exemplary high bar when it comes to making their own mouse models available as soon as they publish.

In some cases sharing the mouse has even preceded publication. Last year Nature reported on a situation regarding a Rett mouse that had been developed by Novartis. The model had been engineered so the Rett protein glowed so it could be tracked visually.  Many researchers were eager to access the model but could not due to legal issues. (Nature article – Licence rules hinder work on rare disease.  Animal model off-limits to Rett syndrome researchers.)  I knew that Adrian Bird after being denied access had created his own model and I asked him whether he would be willing to share it through Jax. He agreed immediately even though he had not published yet. The mouse is now available to any researcher worldwide that needs it.

Besides teaching us about the molecular underpinnings of disease, mouse models may be effective to test treatments.  We have all heard many stories about how drugs tested in mice with success are found to be ineffective in humans. The next few years will be extremely interesting as we begin to explore how predictive the Rett mice models really are.