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Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice.

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.

journal_name

Immunity

journal_title

Immunity

authors

Vanden Berghe T,Hulpiau P,Martens L,Vandenbroucke RE,Van Wonterghem E,Perry SW,Bruggeman I,Divert T,Choi SM,Vuylsteke M,Shestopalov VI,Libert C,Vandenabeele P

doi

10.1016/j.immuni.2015.06.011

subject

Has Abstract

pub_date

2015-07-21 00:00:00

pages

200-9

issue

1

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(15)00254-X

journal_volume

43

pub_type

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