Functional analysis of secreted and transmembrane proteins critical to mouse development

Nat Genet. 2001 Jul;28(3):241-9. doi: 10.1038/90074.


We 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Breeding
  • Genes, Lethal
  • Genetic Vectors
  • Genotype
  • Membrane Proteins / genetics*
  • Mice / genetics*
  • Molecular Biology / methods*
  • Mutagenesis, Insertional
  • Phenotype
  • Polymerase Chain Reaction
  • Proteins / metabolism*
  • Selection, Genetic
  • Sequence Tagged Sites
  • Stem Cells / cytology


  • Membrane Proteins
  • Proteins