Longer-Lived Mouse Model Improved Tool for Biliary Atresia Research
Published April 2020 | Hepatology
In recent years, biliary atresia (BA) research has been hampered because the primary mouse model of the disease had a 14-day lifespan. But now, a new method of inducing a biliary atresia-like state in mice has resulted in longer survival times and more opportunity to study potential medications.
Biliary atresia is the leading cause of liver transplantation for children. Inflammation from the condition results in end-stage liver disease and, without surgical intervention, leads to death by 2 years of age. Experts have long suspected that a prenatal viral infection might trigger the bile duct blockages the condition induces.
So far, scientists have used a rhesus rotavirus to induce biliary obstruction that parallels human biliary atresia. But the liver damage is so extensive that mice die within 14 days. The Cincinnati Children’s team—led by first and corresponding author Sujit Mohanty, DVM, PhD, and senior author Greg Tiao, MD—generated an RRV-TUCH rotavirus reassortant that resulted in longer-lived mouse models.
Their study shows that the new mouse model shows increased cholangiocyte proliferation, extensive liver fibrosis, and partial bile duct obstruction that better mimic the disease progression seen in humans. Importantly, the team compared genetic data from patients with BA and found that the new mouse model shares an expression pattern involving several genes linked to human BA.
“This model of rotavirus-induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies to identify therapeutic targets that may alter the course of biliary atresia,” the co-authors say.
