[/fusion_text][fusion_text] A RARE but potentially life-threatening genetic disorder, known as Alagille syndrome, is associated with chronic liver and heart problems in children. Little is understood regarding how the disease develops, and symptoms are currently treated separately. Now, researchers have found that the mutation of JAGGED1, often connected to the condition, not only affects the development of specific cell types, it also controls the formation of the liver’s bile ducts. Each year, a small number of children are born and diagnosed with Alagille syndrome. Symptoms are vast and wide-reaching, and heart and liver problems can sometimes be so severe that a transplant is required. Other symptoms include deformities in eyes or bones, growth disorders, and itchiness resulting from associated liver problems. Researchers at the Karolinska Institute, Stockholm, Sweden, through the aid of a new mouse model, have discovered how the syndrome’s corresponding liver issues result from incorrect formation of the bile ducts. The researchers utilised mice and created JAGGED1 mutants with similar liver and heart problems through single-point amino acid mutations in the Notch ligand, the protein produced by the JAGGED1 gene. They found that a specific single point mutation produced an interference in the Notch signalling system. Communication between Notch ligand and Notch receptor 1 was altered; however, communication with Notch receptor 2 appeared to be unchanged. Prof Emma Andersson, Department of Biosciences and Nutrition, Karolinska Institute, noted: “We hope to be able to use our mouse model to understand the disease better, predict which children will need a transplant, and ultimately find a cure.” To verify whether the findings were relevant to humans, liver biopsies were donated from Alagille patients and RNA sequenced for comparison with the Human Protein Atlas. The results showed that the findings were indeed transferrable: “We have been able to identify new markers for the bile ducts that confirm the malformations that develop in patients with Alagille Syndrome,” explained Prof Emma Anderson. The researchers hope that this discovery will open up more avenues for more specific treatment of this rare and dangerous condition.