Functional Mx protein does not prevent experimental biliary atresia in Balb/c mice.
Biliary atresia (BA) is a rare cholestatic disease, which manifests itself in the form of inflammation of the liver and bile ducts in newborns, with an unknown etiology and a poor outcome. Mx proteins, which are mediators of innate, antiviral resistance induced by type I interferon, were recently detected in the livers of children with BA. Therefore, the aim of this study was to examine whether the expression of Mx protein could affect the course of experimental BA in mice. A total of 185 newborn Balb/c mice (expressing dysfunctional Mx protein) and Balb/c-Mx+-A2G mice (with functional Mx protein) were intraperitoneally infected with rhesus rotavirus (RRV) or injected with saline solution as controls. They were sacrificed if they showed signs of cholestasis or at three weeks after infection. The expression of hepatic Mx protein was detected by immunostaining (POX) and the hepatic virus load was determined. There was no significant difference in the incidence of cholestasis between wild-type Balb/c mice and Balb/c-Mx+-A2G mice (67 % vs. 65 %). However, Mx protein was highly expressed in Balb/c-Mx+-A2G mice with BA phenotype, but not in wild type Balb/c mice or disease-free Balb/c-Mx+-A2G mice despite RRV infection. The difference in the hepatic virus load was not statistically significant in mice with BA. In conclusion, Mx protein does not prevent newborn Balb/c mice from developing biliary atresia after RRV infection. However, the expression of Mx protein is independent of the hepatic virus load and could be used as a marker of BA in humans, as well as in the RRV model.
Wehrmann
F
F
Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
Kuebler
J F
JF
Wienecke
S
S
Al-Masri
A N
AN
Petersen
C
C
Leonhardt
J
J
D000818:Animals; D001656:Biliary Atresia / Q000378:metabolism* / Q000517:prevention & control / Q000821:virology; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D016350:Leucine Zippers; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D064547:Myxovirus Resistance Proteins; D011379:Prognosis; D012401:Rotavirus / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000150:complications; D019562:Viral Load
C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins