Technology

Targeted mutagenesis by homologous recombination in Drosophila melanogaster.Rong, Y. S. et al. Genes Dev. 16, 1568–1581 (2002)

Gene targeting by homologous recombination is a recent addition to the fly genetic toolkit. The lab that first described the technique two years ago now successfully addresses its general utility. By using a modified version of the original methods, the authors have generated specific alleles of five genes, using only knowledge of the DNA sequence of the targeted locus. Insertional mutations and allelic substitutions can be easily generated with this technique, except in telomeric regions.

Development

Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial identity.Lee, C. S. et al. Genes Dev. 16, 1488–1497 (2002)

Downstream targets of activated Notch — the proneural genes, such as neurogenin 3, math1 and Neurod — have been shown to drive differentiation of endocrine cells in the gut epithelium. Lee et al. extend these findings by constructing an EGFP-marked null allele of neurogenin 3. They show that the gene is required for enteroendocrine cell differentiation in the stomach and for the maintenance of gastric epithelial identity.

Cancer Genetics

Mutations of the BRAF gene in human cancer.Davies, H. et al. Nature 9 June 2002 (10.1038/nature00766)

This is the first report from a systematic genome-wide screen for genes that are frequently mutated in cancers. The authors compared genomic DNA from 15 cancer cell lines with normal lymphoblastoid cell lines from the same individuals, focusing on the region around BRAF — a downstream target of RAS. This, and additional analyses, identified mutations in BRAF that associate with cancers, especially with malignant melanomas. Of such melanomas, 66% are positive for a missense BRAF mutation that constitutively stimulates the RAS pathway.

Gene Therapy

Restoration of spermatogenesis by lentiviral gene transfer: offspring from infertile mice.Ikawa, M. et al. Proc. Natl Acad. Sci. USA 99, 7524–7529 (2002) GENE THERAPY

Mice that are mutant for Steel (Sl), which encodes the ligand (Kitl) for the c-kit receptor, are good models for human male infertility, as Kitl is required in Sertoli cells to support normal spermatogenesis. Lentiviral-mediated transfer of functional Kitl to the Sertoli cells of Sl/Sld mice rescued spermatogenesis defects and infertility in all testes studied. None of the sired pups carried the transgene, making lentiviral transmission a possible means to treat human male infertility.