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Mouse strain differences in susceptibility to sporidesmin-induced biliary tract injury
P S Bhathal1, T W Jordan, I R Mackay
1Department of Anatomical Pathology, Royal Melbourne Hospital, Victoria, Australia.
Abstract:
Biliary tract injury was examined in four inbred strains of mice orally dosed with 500 micrograms of the fungal toxin sporidesmin. Semiquantitative histological analysis was used to assess the grade of necroinflammatory changes in the gall bladder, intra- and extrahepatic biliary tree and lobular parenchyma. Injury was greatest in the C57BL/6 and C3H strain mice and was least in SJL/J mice. In these strains injury was greatest at 4 days and had regressed by 10 days. In BALB/c mice the damage, although similar to that in SJL/J mice at 4 days, persisted at the same severity at day 10 and was accompanied by periductal fibrosis and occasionally by obliteration of ducts typical of sclerosing cholangitis. Analysis of the time-course of development of the lesions in C57BL/6 mice showed that the primary target for the toxin is the biliary epithelium. The severity of the lesions within the liver increased centripetally and the worst affected ducts were found at the confluence of the lobar ducts with the common bile duct. The variation in the degree of damage and rate of healing between strains may be due to differences in sporidesmin excretion in bile or interactions with biliary epithelial cells and/or efficacy of protective cellular repair mechanisms.
Insights
Fungal toxin sporidesmin causes biliary tract injury in mice, with varying severity and healing rates across different strains. BALB/c mice showed persistent damage resembling sclerosing cholangitis.
Area of Science:
- Toxicology
- Hepatology
- Gastroenterology
Background:
- Sporidesmin is a fungal toxin known to cause liver and biliary damage.
- Inbred mouse strains exhibit genetic variations that can influence susceptibility to toxins.
Purpose of the Study:
- To investigate the effects of sporidesmin on the biliary tract in different mouse strains.
- To characterize the histological changes and time-course of injury induced by sporidesmin.
- To explore strain-dependent variations in response to sporidesmin toxicity.
Main Methods:
- Oral administration of 500 micrograms of sporidesmin to four inbred mouse strains (C57BL/6, C3H, SJL/J, BALB/c).
- Semiquantitative histological analysis of the gallbladder, intrahepatic and extrahepatic biliary tree, and liver parenchyma.
- Time-course analysis of lesion development in C57BL/6 mice.
Main Results:
- Significant biliary tract injury was observed, with C57BL/6 and C3H strains showing the greatest damage, and SJL/J the least.
- BALB/c mice exhibited persistent biliary damage by day 10, including periductal fibrosis and duct obliteration, indicative of sclerosing cholangitis.
- Histological analysis revealed biliary epithelium as the primary target, with injury severity increasing centripetally towards the common bile duct.
Conclusions:
- Mouse strain genetic background significantly influences the susceptibility and response to sporidesmin-induced biliary injury.
- Differences in sporidesmin excretion, epithelial cell interactions, or repair mechanisms may explain observed inter-strain variations.
- BALB/c mice are particularly susceptible to chronic biliary damage and fibrosis following sporidesmin exposure.