Elizabeth Ross, M.D., Neurology Dept., (612) 626-2499
Teri Charest, Academic Health Center, (612) 624-4604
BETTER MOUSE MODEL KEY TO UNDERSTANDING NEURAL TUBE DEFECTS
MINNEAPOLIS / ST. PAUL-- The research finding appears in the November issue of Human Molecular Genetics. A strain of Crooked tail (Cd) mice bred by University of Minnesota researchers may help unlock the genetic secrets of neural tube defect (NTD), one of the leading causes of infant mortality. The mice closely mimic humans in the appearance of NTD as well as in their response to folic acid, which is known to reduce the incidence of NTD.
NTD occurs when the neural tube, containing cells that eventually form the brain and spinal cord, fails to seal during fetal development, causing nerve tissue to spill out from either the skull area, a condition called anencephaly, or the backbone, a condition called spina bifida. NTD is believed to affect one in 2,000 births, though it may be higher because accurate counts are not kept in the United States. Anencephaly victims are missing large portions of nerve tissue at birth and die within hours.
The causes of NTD are complex and include genetic predisposition and environmental factors. Folic acid supplements have been shown to reduce the recurrence of NTD as much as 70 percent in mothers with a family history, but it's not known why.
"In producing an animal model that closely parallels the clinical experience of humans, we hope to better understand how folic acid works to prevent NTD," said university neurologist Elizabeth Ross, who directed the research. "Better understanding could lead to more precise ways of predicting its occurrence and tailoring preventative steps for families at risk. Someday we may be able to look at a gene profile to determine whether a family will benefit from folic acid or would be better served by another supplement."
The Cd mouse carries a gene mutation that leads to a crooked tail and an unusually high risk of NTD. It is the first animal model to respond to folic acid diet supplements in the same way humans do. This closer parallel to human characteristics should give scientists a better chance to unravel the biochemical and genetic mysteries surrounding NTD.
Studies on the Cd mice have already answered one question that had been puzzling scientists: Does folic acid reduce the incidence of NTD births by "rescuing" NTD-affected embryos or by promoting their early death? "Our data clearly show folic acid supplements rescue embryos from early lethality," Ross said.
The next step for Ross is to identify the specific Cd gene, which may help explain the complex genetic factors leading to NTD, particularly anencephaly. Her team has narrowed the search to a very specific "address" on mouse chromosome 6, and they hope to identify the gene within the year. Then it's a matter of determining whether that same gene is involved in human families affected by NTD.
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