A team of researchers at the CSIC/University of Salamanca and the Centro Nacional de Investigaciones Oncológicas, Spain, has developed a new mouse model of Costello syndrome (CS) -- an inherited disorder that affects many parts of the body, causing multiple symptoms; for example, effects on the brain and heart result in mental retardation and structural heart defects, respectively. The authors believe this new mouse model of CS will be useful for evaluating potential therapeutic strategies for individuals with CS, as there is currently no treatment for the disease.
CS is caused by mutations in the H-RAS gene, and the mouse model of CS was generated by engineering mice such that their H-Ras gene contained one of the mutations found in individuals with CS. The mice were found to have many, but not all, of the symptoms of CS. For example, they had abnormally shaped faces and heart defects. The mice also developed high blood pressure as they aged, something that has been documented for few individuals with CS (however, the author speculate that this might have gone undetected because most patients with CS do not undergo regular medical checkups after reaching adulthood).
The high blood pressure was caused by abnormal upregulation of a protein known as Ang II and was prevented by treatment with a drug used to treat individuals with high blood pressure that inhibits the generation of Ang II. As some of the heart defects were also less severe after treatment with the drug, the authors suggested that some of the heart defects might be secondary changes in Ang II expression rather than direct effects of mutation of the H-RAS gene.
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