Nature Genetics
28, 241 - 249 (2001)
doi:10.1038/90074
Functional analysis of secreted and transmembrane proteins critical to mouse developmentKevin J. Mitchell1, 2, 4, Kathy I. Pinson1, 4, Olivia G. Kelly1, Jane Brennan3, Joel Zupicich1, Paul Scherz1, Philip A. Leighton2, Lisa V. Goodrich2, Xiaowei Lu2, Brian J. Avery1, Peri Tate1, Kariena Dill1, Edivinia Pangilinan1, Paul Wakenight1, Marc Tessier-Lavigne2
& William C. Skarnes11
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. 2
Howard Hughes Medical Institute and Department of Anatomy, University of California, San Francisco, California, 94143 USA. 3
Present address: Department of Molecular & Cell Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA. 4
These authors contributed equally to the work.
Correspondence should be addressed to William C. Skarnes skarnes@socrates.berkeley.eduWe describe the successful application of a modified gene-trap approach, the secretory trap, to systematically analyze the functions in vivo of large numbers of genes encoding secreted and membrane proteins. Secretory-trap insertions in embryonic stem cells can be transmitted to the germ line of mice with high efficiency and effectively mutate the target gene. Of 60 insertions analyzed in mice, one-third cause recessive lethal phenotypes affecting various stages of embryonic and postnatal development. Thus, secretory-trap mutagenesis can be used for a genome-wide functional analysis of cell signaling pathways that are critical for normal mammalian development and physiology.
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