Transgenic mouse model of familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited disorder, characterized by the extracellular deposition of amyloid fibrils composed of variant transthyretin (TTR), and by prominent peripheral nerve involvement. We demonstrate that the main cause of this disease is the presence of a point mutation in the TTR gene. However, neither the time of onset nor the clinical course is predictable. To elucidate the molecular pathogenesis of this disease, we constructed transgenic mice carrying and expressing the human mutant TTR gene. In these mice, amyloid is deposited in the alimentary tract as early as age six months, and becomes more remarkable with aging. These transgenic mice should be useful in elucidating factors which modulate the time of onset and the clinical course of FAP, and in establishing therapy for this intractable disorder.