Learning about neurofibromatosis
Type 1 neurofibromatosis (NF1) is a prevalent genetic disorder, affecting about 1 in 3,500 newborns. The syndrome is characterized by tumors of the nervous system and blood; about half of people with NF1 also have learning impairments. The disease is caused by mutations in the gene NF1, which encodes neurofibromin. Neurofibromin is a signaling protein that coordinates information relayed from the cell surface and appropriate cellular response to that information. But, as illustrated by NF1 syndrome, the inactivation of one signaling molecule can result in the disruption of many cellular processes. The challenge, therefore, is to sort out which signaling pathways are responsible for the different aspects of the NF1 syndrome.
A study by Alcino Silva and colleagues (of the University of California, Los Angeles) provides some insight into how neurofibromin mediates the learning process (Nature Genetics, Vol. 27, Issue 4, 01 April 2001). Silva and colleagues engineered mutant mice in which a specific portion of Nf1--exon 23a--has been removed. These mice develop normally, in contrast with those lacking Nf1 (which die in utero). And they do not develop tumors, unlike people with NF1 (who are born with only one copy of functioning NF1) But when Silva and colleagues tested the learning ability of 23a-deficient mice, they observed impairments similar to those affecting people with NF1. As these mice developed normally, it would seem that the learning deficits of NF1 patients are caused by aberrations in brain biochemistry, rather than aberrant development-rendering the prospect of treatment a more realistic one than in the case of developmental glitches. Consistent with this is the finding that the learning impairments of both 23a-deficient mice and NF1 patients can be overcome by extensive training. As pointed out by Yuan Zhu and Luis Parada (of University of Texas Southwestern, Dallas) in an accompanying News & Views article, exon 23 encodes a region of the protein that is likely to disrupt signaling of in a particular pathway, known as the Ras-GAP pathway.
Dr. Alcino Silva
University of California at Los Angeles
Los Angeles, California, USA
Telephone: +1 (310) 794 6345
Fax: +1 (310) 794 7088
Dr. Luis F. Parada
University of Texas Southwestern Medical Center
Dallas, Texas, USA
Telephone: +1 (214) 648 1951
Fax: +1 (214) 648 1960
e-mail Address: email@example.com
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