Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies

Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein-coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits i...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2015-07, Vol.11 (7), p.e1005344
Main Authors: Zhang, Shuxiao, Ross, Kevin D, Seidner, Glen A, Gorman, Michael R, Poon, Tiffany H, Wang, Xiaobo, Keithley, Elizabeth M, Lee, Patricia N, Martindale, Mark Q, Joiner, William J, Hamilton, Bruce A
Format: Article
Language:English
Subjects:
Amygdala - metabolism
Animals
Base Sequence
Behavior
Behavior, Animal - physiology
Cell division
Circadian Rhythm - physiology
Circadian Rhythm Signaling Peptides and Proteins - genetics
Drosophila melanogaster - genetics
Drosophila Proteins - genetics
Fear - physiology
Female
Fruits
Gene Deletion
Genes
Genomes
Grants
Insects
Kinases
Locomotion - genetics
Male
Mammals
Mice
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Mutation
Nerve Tissue Proteins - genetics
Neurosciences
Proteins
Sequence Analysis, DNA
Sex Factors
Sleep - genetics
Sleep - physiology
Studies
Suprachiasmatic Nucleus - metabolism
Vestibular Function Tests
Vestibule, Labyrinth - pathology
Vestibule, Labyrinth - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein-coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits in vestibular function, fear learning and circadian behavior, which correlated with Nmf9 expression in inner ear, amygdala, and suprachiasmatic nuclei. Homologous genes from unicellular organisms and invertebrate animals predict interactions with small GTPases, but the corresponding domains are absent in mammalian Nmf9. Intriguingly, homozygotes for null mutations in the Drosophila homolog, CG45058, show profound locomotor defects and premature death, while heterozygotes show striking effects on sleep and activity phenotypes. These results link a novel gene orthology group to discrete neurological functions, and show conserved requirement across wide phylogenetic distance and domain level structural changes.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1005344