Hypomorphic mutation in hnRNP U results in post-implantation lethality

Transgenic Res. 2005 Apr;14(2):179-92. doi: 10.1007/s11248-004-8147-8.


The present study characterized an embryonic lethal mutation induced by insertion of the U3Neo gene trap retrovirus into an intron of the gene encoding heterogeneous ribonuclear protein U (Hnrnpu), which maps to the distal arm of mouse chromosome 1. Murine hnRNP U was found to be identical to the human protein at all but one of 341 amino acid residues. Embryos homozygous for the provirus showed obvious abnormalities after 6.5 days of development (E6.5) and were resorbed by E10.5. Expression of the inserted neomycin-resistance gene involved alternative splicing to a cryptic 3' splice site located in the neomycin resistance gene resulting in a hypomorphic mutation. Homozygous mutant cell lines isolated from preimplantation blastocysts expressed hnRNP U transcripts at levels 2 to 5 times lower than wild-type cells, suggesting that nearly wild-type levels of hnRNP U are required for embryonic development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Embryo Loss*
  • Embryonic Development / genetics*
  • Gene Expression Regulation, Developmental*
  • Genetic Vectors
  • Heterogeneous-Nuclear Ribonucleoprotein U / genetics*
  • Introns
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Heterogeneous-Nuclear Ribonucleoprotein U