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LBP-1a gene mutation linked to disruption of normal fetal development

The lack of a gene called LBP-1a in the mouse embryo prevents normal growth of blood vessels in the placenta. This finding suggests that a similar defect in humans could play a role in fetal growth retardation, infant mortality and spontaneous abortion. These results, by investigators at St. Jude Children's Research Hospital, are published in the August issue of Molecular and Cellular Biology (MCB). The finding could one day help scientists develop a test to identify women who have this mutation and are at risk for these problems, as well as guide development of new prevention treatments.

The researchers also report that the protein made by the LBP-1a gene is a member of a family of proteins called the "grainyhead transcription factors." This is the first gene-based evidence that a member of this family is essential for normal development of blood vessels outside the growing embryo. A transcription factor is a protein that activates a gene and in this way regulates a specific process.

The study found that mouse embryos lacking the LBP-1a gene were normal during the first 9 days of development, a time during which they survive by exchanging gases, nutrients and toxic breakdown products of food with their outside environment, the amniotic fluid. But embryos lacking LBP-1a failed to produce the extensive network of blood vessels that extends into the part of the developing placenta called the labyrinthine layer and mingles with the sinuses containing blood from the mother. A sinus is a channel inside certain tissues that contains blood.

In the absence of this link to the mother's blood in the placenta, embryos suffered growth retardation by day 10 of pregnancy, and died the next day.

The finding strongly suggests that LBP-1a plays a critical role in the production of blood vessels outside the embryo that extend into the placenta, according to John M. Cunningham, M.D., an associate member of St. Jude Hematology/Oncology. Cunningham is seni
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
6-Aug-2004


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