title: Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies.
abstract: 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.
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Shuxiao
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Ross
authors.affiliation: Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Glen A
authors.initials: GA
authors.lastname: Seidner
authors.affiliation: Department of Psychology, University of California, San Diego School of Medicine, La Jolla, California, United States of America; Center for Circadian Biology, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gorman
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Tiffany H
authors.initials: TH
authors.lastname: Poon
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Keithley
authors.affiliation: Kewalo Marine Lab, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Lee
authors.affiliation: Kewalo Marine Lab, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Mark Q
authors.initials: MQ
authors.lastname: Martindale
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, La Jolla, California, United States of America; Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, California, United States of America; Center for Circadian Biology, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, La Jolla, California, United States of America; Department of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego Moores Cancer Center, and Institute for Genomic Medicine, University of California, San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hamilton
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D005239:Fear / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D008124:Locomotion / Q000235:genetics; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D012890:Sleep / Q000235:genetics / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014724:Vestibular Function Tests; D014722:Vestibule, Labyrinth / Q000473:pathology* / Q000502:physiology
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C000607067:Nmf9 protein, mouse; C000588663:Wake protein, Drosophila