PasSenger Mutations Confound Interpretation Of All Genetically Modified Congenic Mice

Tom Vanden Berghe, Paco Hulpiau, Liesbet Martens, Roosmarijn E. Vandenbroucke, Elien Van Wonterghem, Seth W. Perry, Inge Bruggeman, Tatyana Divert, Sze Men Choi, Marnik Vuylsteke, Valery I. Shestopalov, Claude Libert, Peter Vandenabeele

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Targeted mutagenesis in mice is a powerful tool for functional analysis of genes. However, genetic variation between embryonic stem cells (ESCs) used for targeting (previously almost exclusively 129-derived) and recipient strains (often C57BL/6J) typically results in congenic mice in which the targeted gene is flanked by ESC-derived passenger DNA potentially containing mutations. Comparative genomic analysis of 129 and C57BL/6J mouse strains revealed indels and single nucleotide polymorphisms resulting in alternative or aberrant amino acid sequences in 1,084 genes in the 129-strain genome. Annotating these passenger mutations to the reported genetically modified congenic mice that were generated using 129-strain ESCs revealed that nearly all these mice possess multiple passenger mutations potentially influencing the phenotypic outcome. We illustrated this phenotypic interference of 129-derived passenger mutations with several case studies and developed a Me-PaMuFind-It web tool to estimate the number and possible effect of passenger mutations in transgenic mice of interest.

Original languageEnglish (US)
Pages (from-to)200-209
Number of pages10
JournalImmunity
Volume43
Issue number1
DOIs
StatePublished - Jul 21 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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