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Review
. 2022 Dec:120:103419.
doi: 10.1016/j.dnarep.2022.103419. Epub 2022 Oct 10.

Transgenic mice harboring direct repeat substrates reveal key underlying causes of homologous recombination in vivo

Aimee C Moise  1 , Jennifer E Kay  2 , Bevin P Engelward  3
Affiliations
Review

Transgenic mice harboring direct repeat substrates reveal key underlying causes of homologous recombination in vivo

Aimee C Moise et al. DNA Repair (Amst). 2022 Dec.

Abstract

Homology directed repair is a critical process for maintaining the genome of mammalian cells. While considered to be relatively error free, homologous recombination (HR) can lead to insertions, deletions, translocations, and loss of heterozygosity. Furthermore, it is known that conditions that cause HR events are often carcinogenic, and that HR modulates susceptibility to cancer chemotherapeutics, making HR relevant to both cancer etiology and treatment. To learn about HR in vivo, several laboratories have developed mouse models that harbor direct repeat substrates for which HR yields a phenotype that can be visualized by either a change in pigmentation or by expression of a fluorescent protein. An exciting aspect of this work is that it is possible to detect recombinant cells within intact tissues and thus learn about how physiological changes, genes, and exposures modulate HR susceptibility in vivo, as well as which cell types are most susceptible to HR, and the extent to which recombinant cells have undergone clonal expansion. Here, we review progress in studying HR in vivo for four different mouse strains that harbor direct repeat substrates for HR detection, namely the pun mice, the fluorescent yellow direct repeat (FYDR) mice, the EGFP-DR mice, and the ROSA26 direct repeat (RaDR) mice. Key advances in our understanding of fundamental processes that modulate HR susceptibility in vivo are the focus of this review.

Keywords: Clonal expansion; Homologous recombination; Mice; in vivo mutations.

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Conflict of interest statement

Conflict of Interest statement The authors declare that there are no conflicts of interest.

Figures

Figure 1.
Figure 1.. Direct repeat substrate design and EGFP signal in ROSA26 Direct Repeat (RaDR) Mice.
A) The direct repeat substrate is comprised of two expression cassettes for EGFP where each coding sequence (green) has different deletions (black box) (not drawn to scale). Gene conversion events can lead to transfer of sequence information from one cassette to the other, reconstituting full length cDNA sequence. B) Misalignment of the direct repeat followed by a crossover during a sister chromatid exchange can lead to triplication with a functional cassette in the middle. C) Misalignment during replication fork repair also leads to triplication with a functional cassette in the middle. D) Freshly obtained pancreatic tissue stained with DAPI shows fluorescent foci for the RaDR mice.
See this image and copyright information in PMC

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