Author                                                                                                                              
 


Mona T. Yazdi

Biological Sciences

Mona Yazdi began her research during her freshman year, eager to take advantage of the opportunity to pursue an interest she had developed early in her life. Intending to move on to medical school after graduation, Mona considers her undergraduate research experience to be a tremendous preparation for her future education. She hopes to be able to make a continuing contribution to the scientific community as she pursues a career as a researcher and physician.triangle.gif (504 bytes)

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Abstract                                                                                                                           
 

Cornelia de Lange Syndrome (CdLS) is a developmental disorder that affects multiple organ systems and can range in severity from undiagnosed to failure to thrive. Incidence of congenital heart defects in people with CdLS is as high as 20–30%, and these defects can range from minor atrial septal defects (ASD) to more serious forms such as Tetralogy of Fallot, which leads to a mixing of oxygenated and deoxygenated blood in the ventricles due to ventricular septal defects (VSD). A majority of CdLS cases are due to mutation in one copy of the Nipped B-like (NIPBL) gene, which encodes a cohesion-associated protein that is conserved among all eukaryotes. In this study we use the FlEx gene-trapping technology to establish conditional alleles of Nipbl in mice. Our initial objectives were to establish the Nipbl FlEx/+ line and then toggle the Nipbl allele in vivo from mutant form to wildtype and then back to mutant form using different recombinases. Nipbl FlEx/+ mice, with the Nipbl FlEx allele in the mutant conformation, displayed many of the phenotypes observed in our original Nipbl RRS564/+ line, making it a reliable model for CdLS. Our second objective was to use the Nipbl FlEx series of alleles to identify in which tissues heart defects initiate during development. We found that lowering levels of Nipbl in the heart leads to large ASDs and VSDs.triangle.gif (504 bytes)

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Faculty Mentor                                                                                                                
 

Anne L. Calof

School of Biological Sciences
 

Cornelia de Lange syndrome (CdLS) is a disabling multisystem genetic disease that results from a deficiency in a protein called NIPBL. Individuals with CdLS show a wide range of physical and cognitive problems, but among the most prevalent are congenital heart defects (CHD). By manipulating NIPBL levels in mouse models of CdLS, using the FLEX multi-allele system that has been developed in the Calof lab, we hope to discover the developmental timepoints and tissues in which deficiencies in NIPBL expression are most critical for proper heart development. This may help us discover times and tissues in which heart development is most sensitive to developmental perturbations and lead to the discovery of new causes—and hopefully cures—of congenital heart defects in all babies. Ms. Yazdi’s work represents an important step toward this goal.triangle.gif (504 bytes)

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