TY - JOUR
T1 - A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration
AU - Chu, Jessie
AU - Hong, Nancy A.
AU - Masuda, Claudio A.
AU - Jenkins, Brian V.
AU - Nelms, Keats A.
AU - Goodnow, Christopher C.
AU - Glynne, Richard J.
AU - Wu, Hua
AU - Masliah, Eliezer
AU - Joazeiro, Claudio A.P.
AU - Kay, Steve A.
PY - 2009/2/17
Y1 - 2009/2/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=60549094028&partnerID=8YFLogxK
U2 - 10.1073/pnas.0812819106
DO - 10.1073/pnas.0812819106
M3 - Article
SN - 0027-8424
VL - 106
SP - 2097
EP - 2103
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -