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Passenger mutations confound interpretation of all genetically modified congenic mice

Tom Vanden Berghe (UGent) , Paco Hulpiau (UGent) , Liesbet Martens (UGent) , Roosmarijn Vandenbroucke (UGent) , Elien Van Wonterghem (UGent) , Seth W Perry, Inge Bruggeman (UGent) , Tatyana Divert (UGent) , Sze Men Choi (UGent) , Marnik Vuylsteke (UGent) , et al.
(2015) IMMUNITY. 43(1). p.200-209
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
INFLAMMASOME, CASPASE-11, GENOME, KNOCKOUT MOUSE, MOUSE STRAINS, MUTAGENESIS, TARGETS, STRESS, PHENOTYPES, ACTIVATION

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Chicago
Vanden Berghe, Tom, Paco Hulpiau, Liesbet Martens, Roosmarijn Vandenbroucke, Elien Van Wonterghem, Seth W Perry, Inge Bruggeman, et al. 2015. “Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice.” Immunity 43 (1): 200–209.
APA
Vanden Berghe, T., Hulpiau, P., Martens, L., Vandenbroucke, R., Van Wonterghem, E., Perry, S. W., Bruggeman, I., et al. (2015). Passenger mutations confound interpretation of all genetically modified congenic mice. IMMUNITY, 43(1), 200–209.
Vancouver
1.
Vanden Berghe T, Hulpiau P, Martens L, Vandenbroucke R, Van Wonterghem E, Perry SW, et al. Passenger mutations confound interpretation of all genetically modified congenic mice. IMMUNITY. 2015;43(1):200–9.
MLA
Vanden Berghe, Tom, Paco Hulpiau, Liesbet Martens, et al. “Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice.” IMMUNITY 43.1 (2015): 200–209. Print.
@article{6972877,
  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.},
  author       = {Vanden Berghe, Tom and Hulpiau, Paco and Martens, Liesbet and Vandenbroucke, Roosmarijn and Van Wonterghem, Elien and Perry, Seth W and Bruggeman, Inge and Divert, Tatyana and Choi, Sze Men and Vuylsteke, Marnik and Shestopalov, Valery I and Libert, Claude and Vandenabeele, Peter},
  issn         = {1074-7613},
  journal      = {IMMUNITY},
  language     = {eng},
  number       = {1},
  pages        = {200--209},
  title        = {Passenger mutations confound interpretation of all genetically modified congenic mice},
  url          = {http://dx.doi.org/10.1016/j.immuni.2015.06.011},
  volume       = {43},
  year         = {2015},
}

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