MicroCT of skeleton can ID even the subtlest birth defects

Technique expected to help scientists test gene function across species

SAN ANTONIO (April 29, 2008)—A technique called microscopic X-ray computed tomography (microCT) is affording scientists the ability to visualize even the subtlest birth defects in prenatal and postnatal bats, mice, opossums and primates, which one day may lead to new understandings about human birth defects, said Charles Keller, M.D., of The University of Texas Health Science Center at San Antonio.

He is corresponding author of a multi-institutional paper on the subject in the May issue of The Anatomical Record. The journal features a microCT image on the cover. (See a low-resolution sample image below.)

“This is a paper about how scientists scrutinize birth defects,” said Dr. Keller, assistant professor of cellular and structural biology at the UT Health Science Center’s Greehey Children’s Cancer Research Institute. “We measured differences in skull and limb shape and length between very different types of animals that are commonly studied by geneticists. These techniques, which we developed, serve as a set of standards for geneticists who wish to assess other important bones, such as the bone that is commonly malformed in cleft palate or other face and skull deformities.”

The genetics revolution is enabling developmental biologists and geneticists to more rapidly conduct a host of gene function experiments, such as changing the expression or activity of a gene to make a limb longer or shorter. By doing this, scientists hope to more precisely determine a gene’s function in both normal and abnormal physiology. “These studies will help us understand birth defects, how to prevent them and how to treat them,” Dr. Keller said.

The paper includes skeletal images of a mouse, a zebrafish, a chicken, a duck, the little brown bat, the African clawed frog, an opossum and the mouse lemur. The research team obtained some of the skeletal specimens from the University of Utah, the Southwest Foundation for Biomedical Research in San Antonio and the Lemur Center at Duke University.

“The microCT is excellent for high-resolution, morphological (structural) study of developing bones without the introduction of artifacts of decalcification and tissue processing,” said Frank J. Weaker, Ph.D., associate professor of cellular and structural biology at the UT Health Science Center. Dr. Weaker is an anatomy lecturer and course director whose own educational approach has been to teach dental and medical students using computed tomography-based three-dimensional images.

The paper includes the contributions of more than a dozen investigators from the Greehey Children’s Cancer Research Institute, the Southwest Foundation for Biomedical Research, the University of Utah and George Washington University. A laureate for the 2007 Nobel Prize in Physiology or Medicine, Mario R. Capecchi, Ph.D., of the Department of Human Genetics at the University of Utah, is a co-author. Dr. Keller joined the UT Health Science Center from Dr. Capecchi’s laboratory in January 2005.

The work was made possible in part by software from the National Institutes of Health National Center for Research Resources (NCRR) Center for Integrative Biomedical Computing.

Numira Biosciences, a company co-founded by Dr. Keller, provided the specimen scanner.

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The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $576 million and 5,000 faculty and staff, the UT Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The UT Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to seven campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields. For more information, visit www.uthscsa.edu.

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