Background. Extrahepatic biliary atresia (EHBA), the etiology of which stil
l remains unclear, occurs exclusively in newborns and has recently been sim
ulated in an animal model. It is possible to trigger an EHBA corresponding
to the human disease by means of intraperitoneal infection of newborn Balb/
c mice with rhesus rotavirus (RRV). The aim of the present study was to det
ermine the conditions and circumstances for inducing biliary atresia in thi
s model focusing on first-line immunological aspects.
Methods. Newborn as well as pregnant Balb/c mice were intraperitonally infe
cted with RRV.
Results. The highest incidence of cholestasis (86%) was achieved by infecti
on with 10(beta)PFU/ml RRV within the first 12 h postpartum, resulting in E
HBA with a lethality of 100%. However, the later the newborn mouse is infec
ted, the less likelihood there is that EHBA is triggered. Additionally, the
incidence of biliary atresia in this model depends on the quantity of the
virus that is given intraperitoneally. However, the development of biliary
atresia is not correlated to the virus in the liver. The antepartum. infect
ion of pregnant mice does not induce EHBA in the offspring. Female mice tha
t are immunized against RRV protect their newborns from developing RRV-indu
ced cholestasis and EHBA. This protection is transmitted transplacentally a
nd not by breast milk.
Conclusion. It is obvious that a temporary immunological gap is essential f
or virally induced EHBA. Further studies should focus on specific parameter
s of the immune system of newborn mice in this biliary atresia model. (C) 2
001 Academic Press.