Hydrocephalus and the Accidental Transgene; Redox RNA; To Be a Bee, but He or She?

Briefs Hydrocephalus and the Accidental Transgene; Redox RNA; To Be a Bee, but He or She? Hydrocephalus and the Accidental Transgene Courtesy of Perry Blackshear, NIEHS A chat in an elevator at the National Institute of Environmental Health Sciences led to the discovery of a protein possibly linked to early brain development. Darryl C. Zeldin mentioned to an NIEHS colleague that a line of transgenic mice created by researchers studying the role of the CYP2J2 enzyme in heart function had developed swollen heads. As young adults the mice experienced rapid neurological decline. Zeldin explains, "In our mice, [CYP2J2] is expressed only in the heart." Therefore, he says, brain damage was likely linked to the location of the transgene insertion in the genome. Zeldin's colleague, Perry Blackshear, director of the NIEHS Office of Clinical Research, discovered that the transgene interrupted the murine RXF4 locus, preventing expression of a novel transcript that his team named RFX4_v3.1 RFX4_v3 proved crucial for normal murine brain development. Disrupting a single copy of the gene prevented formation of the subcommissural organ, which is thought to be critical for normal flow of the cerebrospinal fluid. This failure led to congenital hydrocephalus in 100% of the mice. Knocking out both copies caused severe developmental brain defects and perinatal death. The serendipitous discovery illustrates the value of random murine mutagenesis, which is widely debated, says Tom Curran, director of developmental neurobiology at St. Jude's Children's Hospital in Memphis, Tenn. Curran says, "This could [also] provide a foothold in the understanding of human hydrocephalus." --Paula Park 1. P. Blackshear et al., "Graded phenotypic response to partial and complete deficiency of a brain-specific transcript variant of the winged helix transcription factor RFX4," Development, 130:4539-52, October 2003. Redox RNA Hiroaki Suga and colleagues at the State University of New York at Buffalo have identified an RNA molecule that can catalyze a redox (reduction-oxidation) reaction, further supporting the RNA world theory of prebiotic life. The group generated a random pool of RNA molecules and selected for those that catalyzed the oxidation of a benzyl alcohol derivative in the presence of nicotinamide adenine dinucleotide (NAD+). "Our paper is the first demonstration that [an] RNA ribozyme can catalyze a redox chemistry using NAD," says Suga.1 The work also supports the theory that nucleotide cofactors such as NAD and FAD, the intermediates in protein-catalyzed redox reactions, are evolutionary remnants of the RNA world. This has long been a hypothesis of the prebiotic-origins thinkers, says John Burke, University of Vermont, Burlington. Although not a direct proof of the theory, Suga's paper does show that RNA can catalyze the reaction without proteins. "Here's an RNA, by golly, that's stolen the nucleotide cofactor NAD back [from its protein successors], and is using it successfully," says Michael Yarus of the University of Colorado, Boulder. Suga and colleagues found that reactions occurred only in the presence of zinc, which Burke says is a significant find. "The fact that proteins use zinc for this reaction, and these artificial RNA molecules use zinc for this reaction, [suggests] that the proteins and the RNA really may be using a similar sort of catalytic strategy." --Aileen Constans 1. S. Tsukiji et al., "An alcohol dehydrogenase ribozyme," Nat Struct Biol, 10:713-717. Sept. 1. 2003. To Be a Bee, but He or She? Courtesy of Chip Taylor Bees, wasps, and ants have a haplodiploid system of sex determination: Unfertilized eggs remain haploid and develop as males, while fertilized eggs become diploid and female. Recently, researchers from Martin Luther University in Germany, the University of California, Davis, and the Agricultural University of Norway have identified the gene behind bee gender: complementary sex determiner or csd.1 The csd gene has 19 alleles; femaleness requires two different ones. When the researchers blocked expression of one allele in fertilized eggs, the insects developed male gonads. "The csd protein is active if the polypeptides derive from different alleles," says Martin Beye, from Martin Luther. Robert Page, from UC-Davis, speculates that the putative heterodimer binds a third, unknown protein. "That protein then splices together a female-specific active form of something else, which unlocks the female determining cascade." Although haplodiploid sex determination has stood the test of evolution, it has stymied beekeepers, because inbreeding spawns doomed homozygotes. "These diploid males are recognized as such by workers and are eaten," says Thomas Gregg, professor of zoology at Miami University in Oxford, Ohio. The system prevents breeding to fix desired genes, "because colonies of inbred bees are subviable," says Kim Fondrk, staff research associate at UC-Davis. At least now they know why their efforts fail. --Ricki Lewis 1. M. Beye et al., "The gene csd is the primary signal for sexual development in the honeybee and encodes an SR-type protein," Cell, 114:419-29, Aug. 22, 2003. 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

Hydrocephalus and the Accidental Transgene; Redox RNA; To Be a Bee, but He or She?

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Hydrocephalus and the Accidental Transgene; Redox RNA; To Be a Bee, but He or She?

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