Genomes and Genes
Gene Symbol: Dync1h1
Description: dynein cytoplasmic 1 heavy chain 1
Alias: 9930018I23Rik, AI894280, DHC1, DHC1a, DNCL, Dnchc1, Dnec1, Dnecl, Loa, MAP1C, P22, Swl, mKIAA0325, cytoplasmic dynein 1 heavy chain 1, cytoplasmic dynein heavy chain 1, dynein heavy chain, cytosolic, dynein heavy chain, retrograde transport, dynein, cytoplasmic, heavy chain 1, legs at odd angle, sprawling
- Dupuis L, Fergani A, Braunstein K, Eschbach J, Holl N, Rene F, et al. Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease. Exp Neurol. 2009;215:146-52 pubmed publisher..Altogether, these findings show that dynein heavy chain mutation triggers sensory neuropathy rather than motor neuron disease. ..
- Achilli F, Boyle S, Kieran D, Chia R, Hafezparast M, Martin J, et al. The SOD1 transgene in the G93A mouse model of amyotrophic lateral sclerosis lies on distal mouse chromosome 12. Amyotroph Lateral Scler Other Motor Neuron Disord. 2005;6:111-4 pubmed..We have analysed data from a SOD1G93AxLoa cross and determined that the site of the transgene insertion lies proximal of the dynein heavy chain gene on mouse chromosome 12. ..
- Pfister K, Shah P, Hummerich H, Russ A, Cotton J, Annuar A, et al. Genetic analysis of the cytoplasmic dynein subunit families. PLoS Genet. 2006;2:e1 pubmed
- Harada A, Takei Y, Kanai Y, Tanaka Y, Nonaka S, Hirokawa N. Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. J Cell Biol. 1998;141:51-9 pubmed..Moreover, cDHC is required for cell proliferation and proper distribution of endosomes and lysosomes. However, molecules other than cDHC might mediate attachment of the Golgi complex and endosomes/lysosomes to microtubules. ..
- Ilieva H, Yamanaka K, Malkmus S, Kakinohana O, Yaksh T, Marsala M, et al. Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death. Proc Natl Acad Sci U S A. 2008;105:12599-604 pubmed publisherDominant mutations in cytoplasmic dynein (Loa or Cra) have been reported to provoke selective, age-dependent killing of motor neurons, while paradoxically slowing degeneration and death of motor neurons in one mouse model of an inherited ..
- Narayan D, Desai T, Banks A, Patanjali S, Ravikumar T, Ward D. Localization of the human cytoplasmic dynein heavy chain (DNECL) to 14qter by fluorescence in situ hybridization. Genomics. 1994;22:660-1 pubmed
- Mikami A, Paschal B, Mazumdar M, Vallee R. Molecular cloning of the retrograde transport motor cytoplasmic dynein (MAP 1C). Neuron. 1993;10:787-96 pubmed..Thus, in contrast with cilia and flagella, which contain numerous forms of dynein, our results are consistent with the existence of only a single cytoplasmic dynein heavy chain gene, which appears to produce only a single transcript. ..
- Braunstein K, Eschbach J, Ròna Vörös K, Soylu R, Mikrouli E, Larmet Y, et al. A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons. Hum Mol Genet. 2010;19:4385-98 pubmed publisher..Our study supports a role for dynein dysfunction in the pathogenesis of neurodegenerative disorders of the basal ganglia, such as Perry syndrome and HD. ..
- Perlson E, Jeong G, Ross J, Dixit R, Wallace K, Kalb R, et al. A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. J Neurosci. 2009;29:9903-17 pubmed publisher..Mouse models with defects in the retrograde transport machinery, including the Loa mouse (point mutation in dynein) and the Tg(dynamitin) mouse (overexpression of dynamitin), exhibit mild ..
- Banks G, Fisher E. Cytoplasmic dynein could be key to understanding neurodegeneration. Genome Biol. 2008;9:214 pubmed publisherA new mouse mutation, Sprawling, highlights an essential role for the dynein heavy chain in sensory neuron function, but it lacks the ability of other known heavy-chain mutations to ameliorate neurodegeneration due to defective ..
- Eschbach J, Sinniger J, Bouitbir J, Fergani A, Schlagowski A, Zoll J, et al. Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age. Neurobiol Dis. 2013;58:220-30 pubmed publisherMutations in the DYNC1H1 gene encoding for dynein heavy chain cause two closely related human motor neuropathies, dominant spinal muscular atrophy with lower extremity predominance (SMA-LED) and axonal Charcot-Marie-Tooth (CMT) disease, ..
- Encalada S, Szpankowski L, Xia C, Goldstein L. Stable kinesin and dynein assemblies drive the axonal transport of mammalian prion protein vesicles. Cell. 2011;144:551-65 pubmed publisher..Our data suggest a coordination model wherein PrP(C) vesicles maintain a stable population of associated motors whose activity is modulated by regulatory factors instead of by structural changes to motor-cargo associations. ..
- Tucci V, Achilli F, Blanco G, Lad H, Wells S, Godinho S, et al. Reaching and grasping phenotypes in the mouse (Mus musculus): a characterization of inbred strains and mutant lines. Neuroscience. 2007;147:573-82 pubmed..Moreover, our study supports the validity of the mouse as a model for reaching and grasping studies. ..
- Duchen L. A dominant hereditary sensory disorder in the mouse with deficiency of muscle spindles: the mutant Sprawling. J Physiol. 1974;237:10P-11P pubmed
- Banks G, Bros Facer V, Williams H, Chia R, Achilli F, Bryson J, et al. Mutant glycyl-tRNA synthetase (Gars) ameliorates SOD1(G93A) motor neuron degeneration phenotype but has little affect on Loa dynein heavy chain mutant mice. PLoS ONE. 2009;4:e6218 pubmed publisher..other mutants: the TgSOD1(G93A) model of human amyotrophic lateral sclerosis and the Legs at odd angles mouse (Dync1h1(Loa)) which has a defect in the heavy chain of the dynein complex...
- Eschbach J, Fergani A, Oudart H, Robin J, Rene F, Gonzalez de Aguilar J, et al. Mutations in cytoplasmic dynein lead to a Huntington's disease-like defect in energy metabolism of brown and white adipose tissues. Biochim Biophys Acta. 2011;1812:59-69 pubmed publisher..Here, we observed prominently increased adiposity in mice harboring the legs at odd angles (Loa/+) or the Cramping mutations (Cra/+) in the dynein heavy chain gene...
- Scaravilli F, Duchen L. Electron microscopic and quantitative studies of cell necrosis in developing sensory ganglia in normal and Sprawling mutant mice. J Neurocytol. 1980;9:373-80 pubmedThe percentage of neurons undergoing necrosis during foetal and early post-natal development in normal and Sprawling (Swl) mutant mice was determined...
- Jimenez Mateos E, Wandosell F, Reiner O, Avila J, Gonzalez Billault C. Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. Biochem J. 2005;389:333-41 pubmed..Clearly, the differential binding of these cytoskeletal proteins could regulate the functions attributed to the LIS1-dynein complex, including those related to extension of the neural processes necessary for neuronal migration. ..
- Scaravilli F, Duchen L. The development of sensory ganglion cells in normal and Sprawling mutant mice. J Neurocytol. 1980;9:363-71 pubmedThe foetal and early post-natal development of dorsal root ganglion cells in normal and Sprawling (Swl) mutant mice was studied by light and electron microscopy...
- Cross M, Nguyen T, Bogdanoska V, Reynolds E, Hamilton J. A proteomics strategy for the enrichment of receptor-associated complexes. Proteomics. 2005;5:4754-63 pubmed..This affinity matrix method, using an entire cytoplasmic region, may have relevance for other growth factor receptors. ..
- Toyo oka K, Sasaki S, Yano Y, Mori D, Kobayashi T, Toyoshima Y, et al. Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration. Hum Mol Genet. 2005;14:3113-28 pubmed..Our results suggest that NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function. ..
- Duchen L, Scaravilli F. The structure and composition of peripheral nerves and nerve roots in the Sprawling mouse. J Anat. 1977;123:763-75 pubmedPeripheral nerves and lumbar nerve roots of Sprawling, a neurological mutant mouse, were examined with light and electron microscopy...
- Szpankowski L, Encalada S, Goldstein L. Subpixel colocalization reveals amyloid precursor protein-dependent kinesin-1 and dynein association with axonal vesicles. Proc Natl Acad Sci U S A. 2012;109:8582-7 pubmed publisher..well-correlated with the amount of the light chain of kinesin-1 (KLC1) and the heavy chain of cytoplasmic dynein (DHC1) on vesicles. In addition, genetic reduction of APP diminishes KLC1 and DHC1 levels on APP cargos...
- Labialle S, Yang L, Ruan X, Villemain A, Schmidt J, Hernandez A, et al. Coordinated diurnal regulation of genes from the Dlk1-Dio3 imprinted domain: implications for regulation of clusters of non-paralogous genes. Hum Mol Genet. 2008;17:15-26 pubmed
- Ròna Vörös K, Eschbach J, Vernay A, Wiesner D, Schwalenstocker B, Geniquet P, et al. Full-length PGC-1? salvages the phenotype of a mouse model of human neuropathy through mitochondrial proliferation. Hum Mol Genet. 2013;22:5096-106 pubmed publisher..occurs in Cramping mice, a model of hereditary neuropathy caused by a mutation in the dynein heavy chain gene Dync1h1. The mitochondrial proliferation correlates with post-prandial induction of full-length (FL) and N-terminal ..
- Twelvetrees A, Pernigo S, Sanger A, Guedes Dias P, Schiavo G, Steiner R, et al. The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1. Neuron. 2016;90:1000-15 pubmed publisher..video abstract. ..
- Rashid S, Breckle R, Hupe M, Geisler S, Doerwald N, Neesen J. The murine Dnali1 gene encodes a flagellar protein that interacts with the cytoplasmic dynein heavy chain 1. Mol Reprod Dev. 2006;73:784-94 pubmed..By this assay, the C-terminal part of the cytoplasmic dynein heavy chain 1 was identified as a putative interacting polypeptide of Dnali1...
- Ravikumar B, Acevedo Arozena A, Imarisio S, Berger Z, Vacher C, O Kane C, et al. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat Genet. 2005;37:771-6 pubmed
- Aumais J, Tunstead J, McNeil R, Schaar B, McConnell S, Lin S, et al. NudC associates with Lis1 and the dynein motor at the leading pole of neurons. J Neurosci. 2001;21:RC187 pubmed..These data suggest a biochemical and functional interaction of NudC with Lis1 and the dynein motor complex during neuronal migration in vivo. ..
- Sekita Y, Wagatsuma H, Irie M, Kobayashi S, Kohda T, Matsuda J, et al. Aberrant regulation of imprinted gene expression in Gtl2lacZ mice. Cytogenet Genome Res. 2006;113:223-9 pubmed..Therefore, the paternal or maternal inheritance of the TG results in the down-regulation in cis of either Pegs or Megs, respectively, suggesting that the TG insertion influences the mechanism regulating the entire imprinted region. ..
- Tierling S, Dalbert S, Schoppenhorst S, Tsai C, Oliger S, Ferguson Smith A, et al. High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12. Genomics. 2006;87:225-35 pubmed..1-Mb segment telomeric to Gtl2 in mouse and a homology comparison to the human. Ppp2r5c and Dnchc1 at the telomeric end of the analyzed sequence are biallelically expressed, suggesting that the imprinted domain ..
- Yamada T, Yamanaka I, Nakajima S. Immunohistochemistry of a cytoplasmic dynein (MAP 1C)-like molecule in rodent and human brain tissue: an example of molecular mimicry between cytoplasmic dynein and influenza A virus. Acta Neuropathol. 1996;92:306-11 pubmed..This is an example of molecular mimicry between cytoplasmic dynein and influenza A virus, and the antibody appears to be useful for the localization on cytoplasmic dynein in the central nervous system. ..
- Dixit R, Ross J, Goldman Y, Holzbaur E. Differential regulation of dynein and kinesin motor proteins by tau. Science. 2008;319:1086-9 pubmed publisher..The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport. ..
- Duchen L, Scaravilli F. Quantitative and electron microscopic studies of sensory ganglion cells of the Sprawling mouse. J Neurocytol. 1977;6:465-81 pubmedThe L4-6 sensory root ganglia of young and adult Sprawling (Swl) and normal mice were studied. Cell counts showed a great reduction in the total number of ganglion cells in Swl...
- Ori McKenney K, Vallee R. Neuronal migration defects in the Loa dynein mutant mouse. Neural Dev. 2011;6:26 pubmed publisher..The Loa (Legs at odd angles) mouse with a mutation in the dynein heavy chain has been the focus of an increasing number of ..
- Shen Y, Li N, Wu S, Zhou Y, Shan Y, Zhang Q, et al. Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev Cell. 2008;14:342-53 pubmed publisher..Nudel facilitates cell migration by sequestering Cdc42GAP at the leading edge to stabilize active Cdc42 in response to extracellular stimuli. Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP from Nudel. ..
- El Kadi A, Bros Facer V, Deng W, Philpott A, Stoddart E, Banks G, et al. The legs at odd angles (Loa) mutation in cytoplasmic dynein ameliorates mitochondrial function in SOD1G93A mouse model for motor neuron disease. J Biol Chem. 2010;285:18627-39 pubmed publisher..previously shown that the autosomal dominant Legs at odd angles (Loa) mutation in cytoplasmic dynein heavy chain (Dync1h1) delays disease onset and extends the life span of transgenic mice harboring human mutant SOD1(G93A)...
- Nguyen M, Shu T, Sanada K, Lariviere R, Tseng H, Park S, et al. A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons. Nat Cell Biol. 2004;6:595-608 pubmed..Furthermore, variations in levels of NUDEL correlate with disease progression and NF defects in a mouse model of neurodegeneration. Thus, NUDEL contributes to the integrity of CNS neurons by regulating NF assembly. ..
- Cahana A, Jin X, Reiner O, Wynshaw Boris A, O NEILL C. A study of the nature of embryonic lethality in LIS1-/- mice. Mol Reprod Dev. 2003;66:134-42 pubmed..Lis1(-/-) embryos had significantly smaller trophoblast nuclei than wild-type embryos. The results show that LIS1 expression is required for the continued normal development of the ICM and optimal trophoblast giant cell formation. ..
- Hafezparast M, Brandner S, Linehan J, Martin J, Collinge J, Fisher E. Prion disease incubation time is not affected in mice heterozygous for a dynein mutation. Biochem Biophys Res Commun. 2005;326:18-22 pubmed..dynein is the major retrograde transport molecular motor whose function is impaired in the Legs at odd angles (Loa) mouse due to a point mutation in the cytoplasmic dynein heavy chain subunit...
- Courchesne S, Pazyra Murphy M, Lee D, Segal R. Neuromuscular junction defects in mice with mutation of dynein heavy chain 1. PLoS ONE. 2011;6:e16753 pubmed publisher..Cramping 1 (Cra1/+) and Legs at odd angles (Loa/+) mice, with hypomorphic mutations in the dynein heavy chain 1 gene, which encodes the ATPase of the retrograde ..
- Wiesner D, Sinniger J, Henriques A, DieterlÃ© S, MÃ¼ller H, Rasche V, et al. Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration. Hum Mol Genet. 2015;24:2228-40 pubmed publisher..Collectively, our data suggest that stimulating the autophagy/lysosomal system through appropriate nutritional intervention has significant beneficial effects on motor symptoms of dynein/dynactin diseases even after symptom onset. ..
- Wiggins L, Kuta A, Stevens J, Fisher E, von Bartheld C. A novel phenotype for the dynein heavy chain mutation Loa: altered dendritic morphology, organelle density, and reduced numbers of trigeminal motoneurons. J Comp Neurol. 2012;520:2757-73 pubmed publisher..The dynein heavy chain mutation Loa has been reported to cause degeneration of spinal motor neurons, as well as defects of spinal sensory ..
- Bilsland L, Sahai E, Kelly G, Golding M, Greensmith L, Schiavo G. Deficits in axonal transport precede ALS symptoms in vivo. Proc Natl Acad Sci U S A. 2010;107:20523-8 pubmed publisher..A deficit in axonal transport may therefore be a key pathogenic event in ALS and an early disease indicator of motor neuron degeneration. ..
- Hrabe de Angelis M, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, et al. Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet. 2000;25:444-7 pubmed..Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html). ..
- Loschi M, Leishman C, Berardone N, Boccaccio G. Dynein and kinesin regulate stress-granule and P-body dynamics. J Cell Sci. 2009;122:3973-82 pubmed publisher..Here, we show that impairment of retrograde transport by knockdown of mammalian dynein heavy chain 1 (DHC1) or bicaudal D1 (BicD1) inhibits SG formation and PB growth upon stress, without affecting protein-synthesis ..
- Brook G, Duchen L. End-plates, transmission and contractile characteristics of muscles without spindles in the hereditary sensory neuropathy of the Sprawling mouse. Brain. 1990;113 ( Pt 4):867-91 pubmedIn the mutant mouse Sprawling, a deficiency of sensory ganglion cells is associated with a failure of the development of spindles and tendon organs particularly affecting muscles of the hindleg...
- Kuan A, Chamberlain W, Malkiel S, Lieu H, Factor S, Diamond B, et al. Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies. Immunogenetics. 1999;49:79-85 pubmed..Future studies will determine whether the genetic factors identified in this study are also involved in susceptibility to rheumatic fever. ..
- Zhou B, Cai Q, Xie Y, Sheng Z. Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons. Cell Rep. 2012;2:42-51 pubmed publisher..Our study indicates that Snapin-dynein coupling is one of the primary mechanisms driving BDNF-TrkB retrograde transport, thus providing mechanistic insights into the regulation of neuronal growth and survival. ..
- Zhao J, Wang Y, Xu H, Fu Y, Qian T, Bo D, et al. Dync1h1 Mutation Causes Proprioceptive Sensory Neuron Loss and Impaired Retrograde Axonal Transport of Dorsal Root Ganglion Neurons. CNS Neurosci Ther. 2016;22:593-601 pubmed publisherb>Sprawling (Swl) is a radiation-induced mutation which has been identified to have a nine base pair deletion in dynein heavy chain 1 (DYNC1H1: encoded by a single gene Dync1h1)...