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Gene Linked To Glaucoma, Hydrocephalus, And Other Birth Defects

A gene implicated in hydrocephalus and a number of other birth defects in mice has been discovered by scientists at Vanderbilt University Medical Center, the researchers report in the June 12 issue of the journal Cell.

Working with colleagues in Canada, the researchers have linked mutations in the corresponding human gene to glaucoma, a leading cause of blindness in the United States. The gene, called mouse forkhead 1 (mf1), is also associated with defects in the skeleton, the cardiovascular system and kidneys.

"The gene that we cloned is almost identical in mice and humans," said Brigid L.M. Hogan, Ph.D., Howard Hughes Medical Institute investigator and Hortense B. Ingram Professor of Molecular Oncology. "We are excited because the mutant mice can now be used to understand organ systems in the human."

With roots in a classic scientific finding of more than 50 years ago, the discovery offers a clear example of how basic research may ultimately be connected to human disease in ways that could not be imagined at its beginning.

The new findings build upon the research of Hans Gruneberg, a German-born scientist working in the United Kingdom. In 1943, he was the first to describe a spontaneous mouse mutant known as congenital hydrocephalus (ch). These mutant mice, which died soon after birth, were born with a large swelling of the brain that is filled with cerebrospinal fluid (hydrocephalus). They also have several other abnormalities, including open eyes -- they are usually closed in newborn mice -- a missing sternum and other skeletal defects, and problems with their blood vessels and kidneys.

In the 1970s, scientist Margaret Green, working at the Jackson Laboratory in Bar Harbor, Maine, studied the ch mutant mice and described a malformation in the meninges, the spongy tissue around the brain. This defect prevented the proper flow of the cerebrospinal fluid out of the brain through the meninges and into the blo
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Contact: Cynthia Manley
cynthia.manley@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
12-Jun-1998


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