title: Spongiform degeneration in mahoganoid mutant mice.
abstract: 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.
authors.affiliation: Department of Pediatrics, Department of Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Lu
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Jolly
authors.forename: Adam G
authors.initials: AG
authors.lastname: Eldridge
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Gunn
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003433:Crosses, Genetic; D005260:Female; D015870:Gene Expression; D008025:Ligases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010858:Pigmentation; D011328:Prions / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019076:Transgenes; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: C117928:Atrn protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D011328:Prions; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; C470689:Mgrn1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D008025:Ligases