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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Amino Acid Sequence
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Animals
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Blotting, Northern
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Brain / metabolism
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Brain / pathology*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Crosses, Genetic
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Female
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Gene Expression
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Ligases / metabolism
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Male
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Membrane Proteins / genetics
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Mice
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Mice, Inbred C3H
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Mice, Mutant Strains
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Mice, Transgenic
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Models, Biological
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Molecular Sequence Data
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Mutation*
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Neurodegenerative Diseases / genetics*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / pathology*
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Neurons / metabolism
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Neurons / pathology
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Pigmentation
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Prions / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins / metabolism
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Transgenes
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligases
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Vacuoles / ultrastructure
Substances
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Atrn protein, mouse
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Carrier Proteins
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Membrane Proteins
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Prions
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RNA, Messenger
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Recombinant Fusion Proteins
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Ubiquitin
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Mgrn1 protein, mouse
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Ubiquitin-Protein Ligases
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Ligases