MOUSE MOLECULAR GENETICIST AT TEXAS A&M'S INSTITUTE OF
BIOSCIENCES AND TECHNOLOGY SEARCHES FOR GENETIC SOURCES OF SPINA BIFIDA
Understanding the genetic causes of spina bifida is a research objective of James F. Martin, an assistant professor of medical biochemistry and genetics at Texas A&M University's Institute of Biosciences and Technology. Spina bifida is a severe birth defect in which the spinal canal fails to fuse. There is no treatment for the resulting spinal cord damage. Surgery to correct the defect cannot treat the neurological problems which lead to long term disability. Spina bifida is found in 4.6 of 10,000 live births.
Very little is now known about the molecular causes of this spinal defect and damage to the central nervous system that often results. Prenatal diagnosis of spina bifida is now available, however, and in utero surgical therapies are being investigated. Beyond that, however, if genetically based therapies are going to be developed, it is essential first to understand the molecular mechanisms underlying the congenital deformity.
The degrees of severity associated with spina bifida cover a broad spectrum. In its most benign form, spina bifida occulta, the disease shows few clinical implications. The most extreme form, spina bifida with myeloschisis, results in profound disability--spinal cord damage with resulting paralysis. Because of the various degrees of defect involved with the disease, the causes are complicated and probably involve the interaction of multiple genes and perhaps even environmental factors.
With the help of a research grant from the March of Dimes Birth Defects Foundation, Dr. Martin is trying to find the basic genetic mechanisms that regulate closure of the spinal column during development of the human embryo. To do this, he is using transgenic and gene targeted mice to find the molecular mechanisms controllingcell growth and differentiation in vertebrate embryogenesis.
In previous work, he has demonstrated that mice with a loss-of-function mutationin the prx-1 gene developed multiple craniofacial defects. As well, fifteen percent of the prx-1 mutants had spina bifida with a characteristic dorsal malformation of the lumbar neural arches. Based on that earlier work, Dr. Martin hypothesizes that the prx-1 gene plays an important role in the development of spina bifida. He currently is working on defining the role the prx-1 homeobox gene plays in closure of the spinal column.
Because analysis of animal models for spina bifida have shown that abnormal ties in cell proliferation and cell death can result in the disease, he is also looking for alterations in these cellular processes in the prx-1 mutant mice. Finally, he is trying to identify other genes that interact genetically with prx-1 to control formation of the spine. To do this, he is generating mice that carry compound mutations on both the prx-1 and pax-3 genes. By analyzing the compound mutant mice, he can discover whether these two genes regulate the same pathways during spinal development.
James F. Martin, M.D., Ph.D., mouse molecular geneticist
Institute of Biosciences and Technology, Houston
Phone: 713/677-7558
Fax: 713/677-7512
[email protected]
http://www.tamu.edu/ibt/ibtweb/martin.htm
____________________________________________________________
Kay Kendall, Communications Chief
Texas A&M University's Institute of Biosciences & Technology
2121 W. Holcombe Blvd, Houston TX 77030-3303
Tel. 713-677-7736, Fax 713-677-7512
Email: [email protected]
http://www.tamu.edu/ibt/ibt.htm
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