Of Mice and Children

Despite 50 years of research, the cause of Kawasaki disease (KD), the most common cause of acquired heart disease in children, remains a mystery. Fueled by epidemiological and clinical clues that the disease is triggered by an infectious agent that elicited a dramatic immune response in genetically susceptible children, investigators vigorously searched for the responsible agent.1 Thus far, a long list of discarded pathogens is all that remains of these attempts to find the inflammation-causing agent. Application of reverse genetics to engineer synthetic antibodies to track down a putative new virus has shown some promise, but the agent remains elusive.2Article see p 1542In the absence of knowledge of the etiologic agent, animal models were created that recapitulate the pathological changes observed in human tissues. KD was a prime candidate for modeling: The disease was rarely fatal, so well-preserved autopsy tissues were difficult to find; the primary target of the vasculitis, the coronary arteries, could not be biopsied in living children; and a better understanding of disease pathogenesis was needed to devise new therapeutic approaches. It was in the spirit of meeting these challenges that 2 major mouse models of KD were created. The first, created by …