Deletion of RBP-J within renin cells of SV mice leads to dermatitis. (A-C) Mutant animals from the SV background develop hair loss over their back (A) and cystic nodules on their snouts (B) and tails (C). (D-F) With age, hair loss (D) progresses to ulceration and hyperkeratinization (E,F). Pictures are of the same mous­e at day of life 57 (D), day of life 107 (E) and day of life 155 (F). (G-I) Hematoxylin and Eosin staining demonstrates thickened epidermis and dermis, as well as large cysts and inflammatory infiltrates, in mutant animals (H,I) compared with control animals (G). Scale bars: 200 µm.

Dermatitis in SV mice is due to deletion of RBP-J within progenitor cells of the skin and the MPD is a secondary, reactive process. (A) Renin lineage (GFP⁺) cells are present in the skin of RBP-J^fl/+;Ren1^dCre/+(SV);mTmG control mice (left). The nodular and cystic skin lesions of RBP-J^fl/fl;Ren1^dCre/+(SV);mTmG mutant mice are partially GFP positive, signifying the presence of Cre recombinase and thus deletion of RBP-J within skin lesion cells (right). Scale bars: 200 μm. (B) PCR was performed on genomic DNA from bone marrow cells from control animals, animals with B-cell leukemia and animals with dermatitis/MPD, using primers designed to detect wild-type RBP-J alleles, floxed RBP-J alleles and RBP-J alleles that have undergone Cre-mediated deletion. The bone marrow cells from animals with MPD show predominantly floxed RBP-J alleles, but not deletion alleles, confirming that the myeloid cells have not undergone deletion of RBP-J. (C) Flow cytometry on bone marrow cells from mutant Bl6 animals shows a large population of CD19⁺B220^dim leukemia cells, which are largely GFP positive (left panel). Conversely, the bone marrow from mutant SV mice has an increased population of CD11b⁺Gr1⁺ myeloid cells, which are RFP positive (right panel), and thus have not undergone Cre-mediated recombination of RBP-J.

Bl6 mice have more renin lineage cells within hematopoietic tissues compared with SV mice. (A) Bl6 mice have a trend towards more renin lineage cells (marked by GFP) in the spleen compared with SV mice (P=0.057, Mann–Whitney U-test). There is a non-significant trend towards more renin lineage cells in the bone marrow as well (P=0.076, Mann–Whitney U-test). The sample size for each group is shown. (B) There are more renin lineage cells (GFP⁺) in the peripheral blood of Bl6 mice compared with SV mice throughout life. (C) Immunofluorescent images of renin lineage (GFP⁺) cells in the spleen and liver of newborn SV mice compared with newborn Bl6 mice. Scale bars: 100 µm.