Anyone who spends much time reading mouse genetics literature often comes across “Rosa26” mice. What is Rosa26, and why does it come up so frequently in the literature?
Let’s start with the history of its discovery, because it reveals many of the reasons why the locus is used so widely. Rosa26 (Gt(ROSA)26Sor) was discovered in a gene-trap experiment by Philippe Soriano’s laboratory in 1991. The experimental strategy used a promoter-free retrovirus called “ROSABgal,” which encodes the beta galactosidase reporter. The retrovirus integrated randomly in the genome of mouse embryonic stem cells. One of the random insertions happened to “trap” a previously uncharacterized mouse gene with a promoter that, fortuitously, expressed beta galactosidase throughout the entire embryo. Mice that develop from the gene-trapped stem cells are viable, fertile, and have no apparent abnormalities. Later work showed that the gene trap does not affect the function of the Rosa26 locus in any appreciable way.
Rosa26 is highly expressed in most cells and tissues of the adult mice, although it is expressed at lower levels in some cell types (such as postmitotic neurons). Somewhat confusingly, the locus is still known by its formal gene trap nomenclature (Gt(ROSA)26Sor), even in wildtype mice that do not have the beta galactosidase insertion.
There are several reasons why Rosa26 occurs so frequently in mouse genetics literature. Gt(ROSA)26Sor can be readily modified by homologous recombination in ES cells to express transgenes ubiquitously (more or less) in embryonic and adult mice. There are even ready-made targeting vectors that facilitate genetic modification of the locus. One key advantage of targeting Rosa26 is that the transgene integrates in a defined location on chromosome 6. This contrasts with the classical technique of transgenesis, in which plasmid sequences randomly integrate into the genome. Furthermore, targeted insertions in the locus generally do not affect the viability or fertility of the mouse. The Rosa26 promoter has even been cloned as a bacterial artificial chromosome (BAC), and harnessed to drive ubiquitous expression of other reporter genes in transgenic mice.
The Jackson Laboratory currently distributes over 100 mice that have transgenes inserted in the Gt(ROSA)26Sor locus. Which Rosa26 mice would you like to see added to our collection?