Spongiform Degeneration in mahoganoid Mutant Mice

Abstract

mahoganoid is a mouse coat-color mutation whose pigmentary phenotype and genetic interactions resemble those ofAttractin (Atrn). Atrn mutations also cause spongiform neurodegeneration. Here, we show that a null mutation for mahoganoid causes a similar age-dependent neuropathology that includes many features of prion diseases but without accumulation of protease-resistant prion protein. The gene mutated inmahoganoid encodes a RING-containing protein with E3 ubiquitin ligase activity in vitro. Similarities in phenotype, expression, and genetic interactions suggest that mahoganoidand Atrn genes are part of a conserved pathway for regulated protein turnover whose function is essential for neuronal viability.