title: A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration.
abstract: A mouse neurological mutant, lister, was identified through a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Homozygous lister mice exhibit profound early-onset and progressive neurological and motor dysfunction. lister encodes a RING finger protein, LISTERIN, which functions as an E3 ubiquitin ligase in vitro. Although lister is widely expressed in all tissues, motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Pathological signs include gliosis, dystrophic neurites, vacuolated mitochondria, and accumulation of soluble hyperphosphorylated tau. Analysis with a different lister allele generated through targeted gene trap insertion reveals LISTERIN is required for embryonic development and confirms that direct perturbation of a LISTERIN-regulated process causes neurodegeneration. The lister mouse uncovers a pathway involved in neurodegeneration and may serves as a model for understanding the molecular mechanisms underlying human neurodegenerative disorders.
authors.affiliation: Department of Biochemistry, Institute for Childhood and Neglected Diseases, The Scripps Research Institute, ICND216, 10550 North Torrey Pines Road, La Jolla, CA 90237, USA.
authors.forename: Jessie
authors.initials: J
authors.lastname: Chu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hong
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Masuda
authors.forename: Brian V
authors.initials: BV
authors.lastname: Jenkins
authors.forename: Keats A
authors.initials: KA
authors.lastname: Nelms
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Glynne
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Claudio A P
authors.initials: CA
authors.lastname: Joazeiro
authors.forename: Steve A
authors.initials: SA
authors.lastname: Kay
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons; D005838:Genotype; D006720:Homozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016296:Mutagenesis; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010641:Phenotype; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C539338:Ltn1 protein, mouse; D044767:Ubiquitin-Protein Ligases