Mouse model found for ALS.
Mouse model found for ALS.
复制标题
DOI：
10.1126/science.8209242
复制
发表时间：
1994-06
期刊：
影响因子：
56.9
通讯作者：
J. Marx
中科院分区：
文献类型：
--
作者：
J. Marx
Of all the chronic diseases that afflict hu-mankind, those causing degeneration of the brain and nervous system have been among the most difficult to study-partly because there are few small-animal models that accu-ratelymimic theirpathology andclinical features. Now, a research team led by Mark Gurney ofNorthwestern University Medical School in Chicago may have filled that gap for one of the most devastating neurodegen-erative diseases: amyotrophic lateralsclerosis (ALS). The existence of an animal model offers a rayof hope for understanding the mechanism underlying development of the always-fatal condition, which also goes by the name Lou Gehrig's disease. Gurney and his colleagues, including Northwestern's Haifeng Pu and Arlene Chiu of the Beckman Research Institute of the City of Hope Medical Center in Duarte, California, produced the model by introducing into mice a mutant gene that has been linked to a hereditary form of ALS (see p. 1772). Mice that acquired the gene, which carries the genetic code for an enzyme known as Cu, Zn superoxide dismutase (SOD), developed weakness and neuronal degeneration similar to that of ALS patients. Neurobiologist Donald Price of Johns Hopkins University School of Medicine, who has seen a videotape of Gurney's trans-genic mice, says their clinical signs are just what" you would think they should be" for an ALS model." I'm on such a high about Mark's work," enthuses Price. That high is augmented by work by Price's colleagues, in-cluding Donald Cleveland at Johns Hopkins and Nancy Jenkins of the National Cancer Institute who introduced a different SOD gene mutant into mice; one line of their transgenic mice is beginning to showclinical features similar to those of Gurney's. And at least one additional group, led by Jon Gor-don of Mount Sinai Medical Center in New York City, has found that giving mice a mutant SOD gene can cause them to develop ALS-like features. Neither the Price nor the Gordon groups have yet published their work. Robert Abendroth, who has chaired the research committee of the ALS Association for the past 15 years, describes the Gurney paper as an" important development." Not only does it provide direct evidence that a mutant SOD protein can cause ALS, as the genetic studies indicated, but, Abendroth says, it also provides a much-needed system for determining just how the mutant enzyme brings about the neuronal degeneration of ALS. Indeed, Gurney's work already points to one important conclusion: The mutations apparently confersome new and deleterious activity on SOD rather than causing a loss of
