A Model for Epigenetic Inhibition via Transvection in the Mouse.

Transvection is broadly defined as the ability of one locus to affect its homologous locus Although it was first discovered in the 1950s, there are only two known cases in mammals. Here, we report another instance of mammalian transvection induced by the / system, which is widely used for conditional gene targeting in the mouse. We attempted to use the germline-expressed transgene to engineer a mouse mutation, but observe a dramatic reduction of recombination in mice that inherit an already deleted allele A similar phenomenon has previously been observed with another that is expressed during meiosis: This second example of inhibition reinforces the conclusion that certain meiotically expressed alleles can initiate transvection in mammals. However, unlike the previous example, we find that the inhibition of recombination is not due to DNA methylation. In addition, we demonstrate that inhibition is easily alleviated by adding an extra generation to our crossing scheme. This finding confirms that the sites are inhibited via an epigenetic mechanism, and provides a method for the use of other transgenes associated with a similar inhibition event. Furthermore, the abrogation of inhibition by the simple addition of an extra generation in our crosses establishes a unique mouse system for future studies to uncover the mechanism of transvection in mammals.