Progress in developing animal models for biliary atresia.
Animal models for extrahepatic biliary atresia (EHBA) have failed to simulate the course of the disease. Until now only a few aspects of the entity could be investigated and no model was helpful in discovering the etiology of EHBA. Following the suspicion of a viral and hepatotropic infection, investigations in an infectious mouse model were continued. The results of previous and topical studies are summarized here. Infection of newborn Balb/c-mice with rhesus rotavirus (RRV) leads to cholestasis in 85% of the animals followed by a lethality of 90%. Preparation and histomorphological investigation of liver and ligamentum duodenale reveal EHBA of varying extent. Clinical course and morphological findings in mice are very similar to EHBA in newborn children and the results are presented in a chronological table. Hepatobiliary morbidity and lethality after RRV infection is higher in Balb/c-mice than in other mouse strains. This observation supports the suspicion that immunocompetence might be a determining factor in the etiology of EHBA. Initial therapeutic trials were made using this model by treating infected newborn mice with interferon-alpha (IFN). The prophylactic application of IFN protects the infected mice from cholestatic symptoms and appears to induce partial immunity. Their descendants are protected against the hepatotropic effect of RRV infection. Infected animals presenting with clinical signs of cholestasis can be treated successfully by IFN-therapy for one week. In the presented animal model. EHBA can be better induced and simulated than by any other method. As a first trial, a non-surgical and more etiologically orientated therapeutic method is tested in this model.
Department of Pediatric Surgery, Medical School Hannover, Germany.
C
C
Petersen
M
M
Kuske
E
E
Bruns
D
D
Biermanns
P V
PV
Wussow
H
H
Mildenberger
D000818:Animals; D000831:Animals, Newborn; D017734:Bile Ducts, Extrahepatic / Q000276:immunology / Q000473:pathology; D001656:Biliary Atresia / Q000276:immunology / Q000473:pathology*; D001651:Cholestasis, Extrahepatic / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007370:Interferon Type I / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011994:Recombinant Proteins; D012400:Rotavirus Infections / Q000276:immunology / Q000473:pathology
D007370:Interferon Type I; D011994:Recombinant Proteins