Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelin signaling pathway plays an important role in the migration, proliferation, and differentiation of neural crest cells. Mutations in the gene encoding the endothelin receptor type B (EDNRB) cause three symptoms: aganglionosis, pigmented disorder and hearing loss. In addition, the Ednrb null mice show abnormal splenic microarchitecture with lymphopenia. In this study, we examined whether similar phenotypes are reproduced in three Ednrb-null rat strains that we established previously. AGH-Ednrb(sl)/(sl) strain showed a low white blood cell count, significant size reduction and abnormal microarchitecture of spleen. Thymus displayed a marked reduction in the size, but maintained a normal CD4/CD8 ratio. In contrast, splenic cellularity was reduced to < 15%, and splenic B and T cell numbers were reduced, showing a splenic lymphopenia. Interestingly, Ednrb-null rats in the LE and F344 genetic background did not show these abnormalities. These data show that proper T and B cell development is dependent on the endothelin signaling pathway, however, modifier gene(s) might be differentially expressed in these strain to modulate or compensate for the effect of the Ednrb deficiency.
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PMID:Lymphopenia in Ednrb-deficient rat was strongly modified by genetic background. 2297 36

Potentially life-threatening enterocolitis is the most frequent complication in children with colonic aganglionosis (Hirschsprung disease, HSCR), and little is known about the mechanisms leading to enterocolitis. Splenic lymphopenia has been reported in the Endothelin Receptor B (Ednrb)-null mouse model of HSCR that develops enterocolitis. In this study, we sought to identify molecular mechanisms underlying this immune phenotype. We employed the Ednrb(-/-) mouse, and the knockout of its ligand, Edn3 (Edn3(-/-)). The major finding is that enterocolitis in the Ednrb(-/-) and Edn3(-/-) mice lead to thymic involution, splenic lymphopenia, and suppression of B lymphopoiesis as a consequence of colonic aganglionosis, not an intrinsic Edn3-Ednrb signaling defect directly affecting the lymphoid organs. We showed that adoptive transfer of Ednrb(-/-) marrow repopulated the RAG2-null mice marrow, thymus and spleen without development of enterocolitis. We identified the glucocorticoid corticosterone, as a potential mediator of the immune phenotype. This previously unrecognized pattern of immune abnormalities in mouse is nearly identical to lymphoid depletion in neonatal sepsis during severe physiological stress, suggesting that the mouse model used here could be also used for sepsis studies.
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PMID:Enterocolitis causes profound lymphoid depletion in endothelin receptor B- and endothelin 3-null mouse models of Hirschsprung-associated enterocolitis. 2548 64