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• W2005201799 abstract "PurposeThe aim of the study was to describe and characterize a novel small spleen phenotype with splenic lymphopenia in the Ednrb-null (Ednrb−/−) mouse with aganglionosis known to also develop enterocolitis.MethodsWe compared spleen weight as a percent of body weight from Ednrb+/+, Ednrb+/−, and Ednrb−/− mice to quantify our initial observation. Splenic microarchitecture of Ednrb+/+ and Ednrb−/− mice was assessed using both H and E staining and immunofluorescence staining for CD45R+ (B cells) and CD3+ (T cells) on tissue sections. To identify and quantify cell type, flow cytometry for CD19+ (mature B cells), CD4+ and CD8+ (T cells) was performed on the splenocytes of Ednrb+/+ and Ednrb−/− mice and compared with student’s t test. A separate cohort of Ednrb+/+ and Ednrb−/− mice was killed and splenocytes were analyzed by flow cytometry, and proximal colon was histopathologically graded for enterocolitis. Spearman’s rank correlations comparing total splenocyte and CD19+ cell counts with enterocolitis scores were performed.ResultsWe found that the mean spleen weight expressed as a percent of body weight for Ednrb+/+ and Ednrb−/− mice was 0.72 and 0.25%, respectively (P < 0.001), at 25 days of age. In addition, the Ednrb−/− spleens also had markedly abnormal splenic microarchitecture with lymphopenia, and relative reduction of B cells compared to T cells. FACS of splenocytes revealed a 5 to 20-fold reduction in total cell number, CD19+, CD4+, and CD8+ of the Ednrb−/− mice compared to the Ednrb+/+ littermates (P < 0.01). We also found a strong inverse correlation of total spleen and CD19+ cell counts with histopathological enterocolitis scores (r s = −0.43, P = 0.02), showing that mice with reduced cell counts also had increased severity of enterocolitis.ConclusionThe small spleen immunophenotype in the Ednrb−/− mouse suggests that Ednrb-dependent signaling may be required for normal spleen development. These results raise the possibility that primary immune abnormalities may contribute at least in part to some enterocolitis. At present, our data suggest intriguing new potential explanations for HAEC in Hirschsprung patients." @default.
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• W2005201799 date "2010-11-03" @default.
• W2005201799 modified "2023-10-17" @default.
• W2005201799 title "Splenic lymphopenia in the endothelin receptor B-null mouse: implications for Hirschsprung associated enterocolitis" @default.
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• W2005201799 doi "https://doi.org/10.1007/s00383-010-2787-y" @default.
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