SMS Mouse Model
The Lupski lab focuses on studying the genetic mechanisms of and therapies for genomic disorders (i.e. disorders caused by losses or gains of segments of a chromosome). One of the genomic disorders the lab studies is Smith-Magenis Syndrome, which is caused by the constitutional loss of a portion of chromosome 17 (17p11.2). Multiple approaches are utilized to study SMS, including studies on SMS patient DNA samples, as well as on the lab's mouse models of SMS.
The Lupski lab has collected over 130 blood samples from unrelated families with a patient with SMS, and is continually accepting new samples. These samples are used to characterize the molecular properties of the deletions seen in individual patients, and this information is used to help the patient better understand their genetic disorder. These studies are also benefiting the research community by improving the knowledge of the mechanisms by which these deletions and other similar genomic disorders occur.
The mouse models were generated using both chromosome-engineering and gene knock-out approaches. As a result, there are mice that posses a deletion on mouse chromosome 11 (which is very similar to the SMS deletion region on human chromosome 17), as well as mice that have a mutation in one copy of the gene RAI1, which is similar to the situation in patients with RAI1 point mutations. The lab utilizes these mice to study the symptoms of SMS, including those involving metabolism, behavior, circadian rhythms (sleep/wake cycles), physical (developmental) malformations, and immunology. The information gained from this study helps to better understand the symptoms of SMS and to identify potential therapies that may help treat some of these symptoms. Also, methods in molecular biology and biochemistry are used to try and identify the underlying cause at the cellular and molecular level that results in these symptoms. This information may lead to the identification of drug targets or other therapies that may potentially mitigate some aspects of SMS in the future.
To learn more about SMS research at Baylor College of Medicine, visit their website at www.bcm.edu/genetics.