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Title
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Passenger mutations confound interpretation of all genetically modified congenic mice
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Immunity. - Cambridge, Mass.
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Publication
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Cambridge, Mass.
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2015
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ISSN
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1074-7613
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DOI
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10.1016/J.IMMUNI.2015.06.011
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Volume/pages
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43
:1
(2015)
, p. 200-209
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ISI
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000360101100021
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Full text (Publisher's DOI)
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