NR ANMS
AU He,L.; Lu,X.Y.; Jolly,A.F.; Eldridge,A.G.; Watson,S.J.; Jackson,P.K.; Barsh,G.S.; Gunn,T.M.
TI Spongiform degeneration in mahoganoid mutant mice
QU Science 2003 Jan 31; 299(5607): 710-2
PT journal article
AB mahoganoid is a mouse coat-color mutation whose pigmentary phenotype and genetic interactions resemble those of Attractin (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 in mahoganoid encodes a RING-containing protein with E3 ubiquitin ligase activity in vitro. Similarities in phenotype, expression, and genetic interactions suggest that mahoganoid and Atrn genes are part of a conserved pathway for regulated protein turnover whose function is essential for neuronal viability.
MH Alleles; Amino Acid Sequence; Animal; Blotting, Northern; Brain/metabolism/*pathology; Carrier Proteins/chemistry/*genetics/*metabolism; Crosses, Genetic; Female; Gene Expression; Ligases/metabolism; Male; Membrane Proteins/genetics; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Mice, Transgenic; Models, Biological; Molecular Sequence Data; *Mutation; Neurodegenerative Diseases/*genetics/metabolism/*pathology; Neurons/metabolism/pathology; Pigmentation; Prions/metabolism; RNA, Messenger/genetics/metabolism; Recombinant Fusion Proteins/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transgenes; Ubiquitin/metabolism; Vacuoles/ultrastructure
AD Department of Pediatrics, Department of Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
SP englisch
PO USA