title: Lymphopenia in Ednrb-deficient rat was strongly modified by genetic background.
abstract: 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.
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo, Hokkaido, Japan.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Dang
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishino
authors.forename: Moe
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Torigoe
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D016516:CD4-CD8 Ratio; D016232:Endothelins / Q000378:metabolism; D005434:Flow Cytometry; D060045:Genes, Modifier; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics; D018655:Lymphocyte Count / Q000379:methods; D008231:Lymphopenia / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009929:Organ Size; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011916:Rats, Inbred F344; D044023:Receptor, Endothelin B / Q000235:genetics*; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
chemical_list: D016232:Endothelins; D044023:Receptor, Endothelin B