Homemade Mice

We currently have several lines of mice that target Langerhans Cells.   These mice have all been generated using human genomic DNA that contains the gene for langerin.  In mice, human Langerin is expressed only by epidermal Langerhans cells.  Langerin expressing cells other than Langerhans cells (e.g. Langerin+ dermal DC) that have been identified in mice do not express the human Langerin transgene.  As a result, we are able to selectively manipulate Langerhans cells without affecting other DC populations.

Langerin-DTA mice constitutively express the active subunit of diphtheria toxin in LC.  As a result, these mice have a constitutive and durable absence of LC.  These mice develop exaggerated skin responses due to increased development of Th1/Th17 effectors.  These mice are available from JAX.

Langerin-Cre mice express the Cre recombinase in LC.  When these mice are bred with other strains that have floxed genes of interest, the result is a LC-specific knock out of specific genes. LC-specific knockouts of MHC-II and IL-10, like Langerin-DTA, develop exaggerated skin responses and increased T effectors.  Thus, LC-mediated suppression requires cognate interaction with CD4 and elaboration of IL-10.  We have also knocked-out TGFb from LC and found that autocrine TGFb is required for LC development.

Langerin-DTR mice express the primate diphtheria receptor on LC.  Mice are normally resistant to diphtheria toxin.  Cells that express the receptor become susceptible.  Thus, Langerin-DTR mice allow for the selective and inducible depletion of LC by the administration of DT.  Work on these mice is ongoing but it appears that inducible ablation of LC also leads to exaggerated skin immune responses.

Langerin-Cre-ERT2 mice express an inducible form of Cre.  These mice allow for the inducible and LC specific ablation of genes of interest.  These mice are being used to examine LC lineage, migration and induction of tolerance.  These mice are available from JAX.