title: Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse.
abstract: The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system.
authors.affiliation: Department of Neurodegenerative Disease, Medical Research Council Centre for Neuromuscular Diseases, University College London Institute of Neurology, London WC1N 3BG, United Kingdom.
authors.forename: Gareth T
authors.initials: GT
authors.lastname: Banks
authors.forename: Matilda A
authors.initials: MA
authors.lastname: Haas
authors.forename: Samantha
authors.initials: S
authors.lastname: Line
authors.forename: Hazel L
authors.initials: HL
authors.lastname: Shepherd
authors.forename: Mona
authors.initials: M
authors.lastname: Alqatari
authors.forename: Sammy
authors.initials: S
authors.lastname: Stewart
authors.forename: Ida
authors.initials: I
authors.lastname: Rishal
authors.forename: Amelia
authors.initials: A
authors.lastname: Philpott
authors.forename: Bernadett
authors.initials: B
authors.lastname: Kalmar
authors.forename: Anna
authors.initials: A
authors.lastname: Kuta
authors.forename: Michael
authors.initials: M
authors.lastname: Groves
authors.forename: Nicholas
authors.initials: N
authors.lastname: Parkinson
authors.forename: Abraham
authors.initials: A
authors.lastname: Acevedo-Arozena
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: David
authors.initials: D
authors.lastname: Bannerman
authors.forename: Linda
authors.initials: L
authors.lastname: Greensmith
authors.forename: Majid
authors.initials: M
authors.lastname: Hafezparast
authors.forename: Martin
authors.initials: M
authors.lastname: Koltzenburg
authors.forename: Robert
authors.initials: R
authors.lastname: Deacon
authors.forename: Mike
authors.initials: M
authors.lastname: Fainzilber
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001216:Asparagine / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D056445:Cytoplasmic Dyneins / Q000235:genetics*; D003712:Dendrites / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins; D009431:Neural Conduction / Q000235:genetics; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011597:Psychomotor Performance; D018709:Statistics, Nonparametric; D014443:Tyrosine / Q000235:genetics; D014891:Weight Lifting / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D001216:Asparagine; C486041:Dync1li1 protein, mouse; D056445:Cytoplasmic Dyneins