Insertional mutagenesis in transgenic mice

Rijkers, Tonnie; Peetz, Astrid; Rüther, Ulrich

doi:10.1007/bf02336773

Cited by 64 publications

(29 citation statements)

References 85 publications

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“…A review of 35 different insertional mutants generated in transgenic mouse lines revealed that some chromosomes are selected more often for illegitimate integration than others, at least in this limited subset. 61 For example, 5/35…”

Section: Illegitimate Integration Sites Are Not Totally Randommentioning

confidence: 99%

“…43,52,60 Another consequence is that the integrated material can interrupt coding sequences. 61 Indeed, an estimated 15% of all transgenic mouse lines studied had incurred mutations due to DNA integration. 50,51 This is a remarkably high rate of induced change, considering that only about 2-3% of the most extensively sequenced mammalian genome (that of homo sapiens) is made up of coding sequences, 62 whose disruption could give rise to a distinct phenotype.…”

Section: Introductionmentioning

confidence: 99%

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Illegitimate DNA integration in mammalian cells

2003

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Foreign DNA integration is one of the most widely exploited cellular processes in molecular biology. Its technical use permits us to alter a cellular genome by incorporating a fragment of foreign DNA into the chromosomal DNA. This process employs the cell's own endogenous DNA modification and repair machinery. Two main classes of integration mechanisms exist: those that draw on sequence similarity between the foreign and genomic sequences to carry out homology-directed modifications, and the nonhomologous or 'illegitimate' insertion of foreign DNA into the genome. Gene therapy procedures can result in illegitimate integration of introduced sequences and thus pose a risk of unforeseeable genomic alterations. The choice of insertion site, the degree to which the foreign DNA and endogenous locus are modified before or during integration, and the resulting impact on structure, expression, and stability of the genome are all factors of illegitimate DNA integration that must be considered, in particular when designing genetic therapies.

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Section: Illegitimate Integration Sites Are Not Totally Randommentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Illegitimate DNA integration in mammalian cells

2003

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“…154) as well as the expression of the transgene itself may also be severely compromised by surrounding elements (variegation effects; Ref. 110). As a solution to this recurring problem single-copy integration of the transgene into a selected site or the use of so-called insulator elements has been described (14,23,36,41,97).…”

Section: Basic Constitutive Transgenic Strategiesmentioning

confidence: 99%

Of mice and models: improved animal models for biomedical research

Bockamp

Maringer

Spangenberg

et al. 2002

Physiological Genomics

147

109

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The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In this review we will focus on practice, pivotal principles, and progress in the rapidly expanding area of conditional mouse technology. The review will also present an internet compilation of available tetracycline-inducible mouse models as tools for biomedical research ( http://www.zmg.uni-mainz.de/tetmouse/ ).

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“…Randomly integrated transgenes can induce insertional mutations in endogenous genes, amplified by severe alterations of flanking chromosomal regions. Although several thousand transgenic lines have been published, the number of reported insertional mutants is very low so far (reviewed by Rijkers et al 1994). Taking into account that only viable and fertile mutants causing strong phenotypes were identified in characterized lines, the real frequency of insertional mutations should clearly be higher.…”

Section: Position Effects On Transgene Expressionmentioning

confidence: 99%