One Link Found, Many to Go; The Rat's Now in the Ring; Red River for a Red Planet

One Link Found, Many To Go Researchers at the UK's Cambridge Institute of Medical Research (CIMR) and Merck & Co. reported a link between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and autoimmunity (H. Ueda et al., "Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease," Nature, e-pub ahead of print, doi:10.1038/nature01621, April 30, 2003). The researchers used positional cloning to search a 330 kb region surrounding the CTLA4 gene for polymorphisms linked to Graves disease, type 1 diabetes, and autoimmune hypothyroidism. The haplotype implicated in all three disorders affected not the amino acid sequence of CTLA-4, which is a negative immune regulator, but rather the relative amounts of mRNA isoforms. The researchers found that the nonobese diabetic mouse phenotype also correlates with an altered ratio of CTLA-4 splice variants. "It points the finger at a form of CTLA-4 that had been recognized before but hadn't been tied in with the basic mechanisms of autoimmunity," notes CIMR's John Todd. One possibility: The imbalance may reduce the amount of soluble CTLA-4, causing increased T-cell activation. The work brings together some old threads, "and extends them mechanis-tically," says the University of Maryland's Alan Shuldiner, who studies the genetics of complex diseases. But Linda Wicker, a recent émigré from Merck to CIMR, advises against pegging clinical hopes on the finding just yet; as many as 20 or 30 other genetic elements may contribute to these diseases. --Josh P. Roberts The Rat's Now in the Ring Anne MacNamara University of Wisconsin-Madison researchers have created what they believe to be the world's first knockout rats (Z. Yunhong et al., "Production of knockout rats using ENU mutagenesis and a yeast-based screening system," Nat Biotech, published online, May 18, 2003). Rats, staples of scientific research, serve as disease models for diabetes and cancer, among others. Their use helps researchers to understand the effects of various pollutants on living systems. But, transgenic rats are scarce and knockouts are virtual unknowns, leaving researchers unable to study the roles played by certain genes. "People have tried to make rat knockouts using mouse technology," says oncology professor and senior author Michael Gould, whose research focuses on breast cancer. Using mouse technology means manipulating embryonic stem cells to create a stable germ line with the deleted gene. For some unknown reason, says Gould, "None of the stem cells go to germ line, so that approach hasn't worked." This is not surprising, he says, because most mouse strains offer similar resistance. So, the researchers "tried to get an alternative technology," says Gould. The team used the powerful mutagen, ENU (N-ethyl-N-nitrosourea) to create mutant rats. Using an efficient yeast assay, the researchers screened for loss-of-function mutations in specific genes. In effect, Gould used genotype rather than phenotype to screen for both Brca1 and Brca2 knockout rats. The licensing arm of the university holds a patent for the method, which has attracted the interest of drug companies and individual researchers, says Gould. --Harvey Black Red River for a Red Planet Courtesy of Carol Stoker, NASA Ames Research Center The Rio Tinto Scientists from NASA and their Spanish colleagues are scoping out land near the Rio Tinto in southwestern Spain--to see whether Mars could support life. The red river derives its hue from iron, which is metabolized by bacteria living deep in the nearby soil. "The conditions of the system are driven by iron microbiology, and Mars is the [red] planet," explains biologist Ricardo Amils of the Centro de Astrobio-logia in Madrid. Because Mars is iron-rich and bacteria on Earth can metabolize iron, it is possible, he and his NASA colleagues speculate, that Mars could support life. "Obviously, this doesn't mean that whatever we learn about the Rio Tinto will happen in Mars," he cautions. Until now, researchers have studied only the river, Amils says. "We are guessing that there is an underground bioreactor, which is anaerobic." Steve Benner, a University of Florida chemist and member of the National Research Council's Committee on the Origins and Evolution of Life, says, "The Rio Tinto ecosystem provides a clearer understanding of the range of environments that life, like we know it on Earth, might survive. The ecosystem includes high acidity, the presence of toxic metals, and an absence of more common terrean life forms." The Spanish-NASA research team is looking for locations to drill and to test drilling equipment that could be used on Mars and capable of penetrating to 100 meters, Amils says. --Harvey Black function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

One Link Found, Many to Go; The Rat's Now in the Ring; Red River for a Red Planet

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