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

doi:10.1016/j.immuni.2015.06.011

Back

Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice

Journal article

Open access

Peer reviewed

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, …

Immunity (Cambridge, Mass.), Vol.43(1), pp.200-209

2015-07-21

DOI: https://doi.org/10.1016/j.immuni.2015.06.011

PMCID: PMC4800811

PMID: 26163370

Abstract

Matrix Metalloproteinase 8 - genetics

Caspases - genetics

Matrix Metalloproteinase 13 - genetics

Genome - genetics

Connexins - genetics

Genotype

Chromosome Mapping

Amino Acid Sequence - genetics

Mutation - genetics

Nerve Tissue Proteins - genetics

Mice, Knockout

Animals

Comparative Genomic Hybridization

Mice, Congenic - genetics

Mice, Inbred C57BL - genetics

Genetic Variation - genetics

Mice

Polymorphism, Single Nucleotide

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.

Files and links (1)

url

https://doi.org/10.1016/j.immuni.2015.06.011View

Published (Version of record) Open

Metrics

14 Record Views

132 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.609 Toll-like Receptors
Web Of Science research areas: Immunology
ESI research areas: Immunology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice
Creators: Tom Vanden Berghe - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium. Electronic address: tom.vandenberghe@irc.vib-ugent.be
Paco Hulpiau - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Liesbet Martens - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Roosmarijn E Vandenbroucke - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Elien Van Wonterghem - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Seth W Perry - Department of Biomedical Engineering, University of Rochester, Rochester NY 14627, USA
Inge Bruggeman - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Tatyana Divert - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Sze Men Choi - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Marnik Vuylsteke - GNOMIXX bvba, Statistics for Genomics, 9000 Ghent, Belgium
Valery I Shestopalov - Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, FL 33136, USA; Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, FL 33136, USA; Department of Cell Biology and Anatomy, Vavilov Institute for General Genetics, Moscow 119333, Russia
Claude Libert - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Peter Vandenabeele - Inflammation Research Center, VIB, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium; Methusalem Program, Ghent University, 9000 Ghent. Electronic address: peter.vandenabeele@irc.vib-ugent.be
Publication Details: Immunity (Cambridge, Mass.), Vol.43(1), pp.200-209
Publisher: United States
Grant note: R21 CA185216 / NCI NIH HHS EY021517 / NEI NIH HHS R01 EY021517 / NEI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Ophthalmology
Language: English
Resource Type: Journal article
PMID: 26163370
PMCID: PMC4800811
Record Identifier: 991031578007602976