A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease...

Irradiated syngeneic wild-type mice developed the same neutrophilic dermatosis-like disease (NDLD) after adoptive transfer of bone marrow cells from Ptpn6(meb2/meb2) mutant mice.

To analyze differentially expressed genes in the bone marrow of mice with NDLD to gain insight into the role of Ptpn6 in myelopoietic bone marrow pathology, and the mechanisms by which Ptpn6 insufficiency in the hematopoietic cells can lead to the development of skin lesions.

As Ptpn6 is involved in a myriad of signaling pathways, we used a global approach with microarray technology for the first time to characterize changes in the bone marrow and skin of motheaten-type mice.

A total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR <0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR <0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated. We found that genes encoding hematopoietic receptors, neutrophil chemoattractants, Toll-like receptors (Tlr1, Tlr2 and Tlr4) and C-type lectin innate immunity receptors (Clec4e, Clec4d, Clec4n, Clec4a2 and Clec4a3) were significantly up-regulated in both NDLD bone marrow and skin. The Il1b gene was also significantly overexpressed in skin samples, confirming the importance of the IL-1/TLR pathway in the development of early skin inflammation in NDLD mice.

Our results suggest that innate immunity genes play a major role in development of neutrophilic dermatosis-like disease in mice.