Click on images for larger views. The lungs were mottled reddish-brown, the spleen was enlarged and the feet had patchy areas of tan, thickened exudative lesions. There was a generalized patchy loss of hair. SHP-1 is a critical negative regulator in multiple signaling pathways in the hematopoietic and immune systems. Viable motheaten mice develop systemic autoimmunity, anemia and immunodeficiency.
Pathology includes severe inflammatory lesions in the skin and lungs.
These lesions, comprised mainly of macrophages and granulocytes, are not associated with infection and occur even under specific pathogen-free husbandry conditions. A number of signaling pathways in monomyeloid cells are regulated through the phosphorylation of tyrosine residues in growth factor receptors and other proteins, resulting in activation of the pathway. The dephosphorylation of tyrosine residues and subsequent deactivation of this pathway maintains normal homeostasis. In viable motheaten mice, which are deficient in SHP-1, tyrosine residues are not dephosphorylated, thus preventing down regulation of the signaling pathway resulting in proliferation of monomyeloid cells. Trichrome staining of lung sections from viable motheaten mice demonstrates increased intra-alveolar and interstitial collagen deposition.