Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice

Citation
K. Ochiai et al., Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice, INT IMMUNOL, 12(1), 2000, pp. 1-8
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOLOGY
ISSN journal
0953-8178 → ACNP
Volume
12
Issue
1
Year of publication
2000
Pages
1 - 8
Database
ISI
SICI code
0953-8178(200001)12:1<1:GROAAA>2.0.ZU;2-Q
Abstract
New Zealand Black (NZB) mice spontaneously produce anti-erythrocyte autoant ibodies (AEA) in association with splenomegaly, thus serving as a model for autoimmune hemolytic anemia, Although these autoimmune traits are inherite d as a dominant fashion, expression in F-1 hybrids of NZB and most non-New Zealand strains is suppressed due to the contribution of wild-type modifyin g genes present in the latter strains. Using chromosomal microsatellite mar kers in the (C57BL/6 x NZB)F-1 x NZB backcross progeny, we mapped C57BL/6 m odifying loci for AEA production and splenomegaly, Generation of AEA was fo und to be down-regulated by a combined effect of two major independently se gregating dominant alleles--one linked to D7MIT30 on chromosome 7 and the o ther linked to D10MIT42 on chromosome 10, Splenomegaly was modified mainly by a single C57BL/6 allele linked to D4MIT58 on chromosome 4, Thus, the aut oimmune hemolytic anemia in the NZB strain is under multigenic control and a combined action of not only susceptibility but also modifying alleles wit h suppressive activities affects the outcome of disease features in the pro geny. There are potentially important candidate genes which may be linked t o the regulation of AEA and splenomegaly.