Research Topics
Genomes and Genes | MIRIAM MEISLERSummaryAffiliation: University of Michigan Country: USA Publications
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Publications
Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8AValerie L Drews
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, 48109 0618, USA
Mamm Genome 18:723-31. 2007..The compact cluster of conserved regulatory elements in SCN8A provides a useful target for molecular analysis of neuronal gene expression...- Ion channel mutations in mouse models of inherited neurological diseaseM H Meisler
Department of Human Genetics, University of Michigan, Ann Arbor 48109 0618, USA
Ann Med 29:569-74. 1997..The mouse studies indicate that mutations in ion channel genes are likely to be responsible for a broad spectrum of clinical phenotypes in human neurological disorders... - Allelic mutations of the sodium channel SCN8A reveal multiple cellular and physiological functionsMiriam H Meisler
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0618, USA
Genetica 122:37-45. 2004..These mutations demonstrate the value of mouse models to elucidate the pathophysiology of human disease... - Gene symbol: SCN8A. Disease: Ataxia. Accession #Hd0520M H Meisler
Department of Human Genetics, University of Michigan, 4909 Buhl, Box 0618, Ann Arbor, MI 48109-0618, USA
Hum Genet 118:776. 2006 - Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALSMiriam H Meisler
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan48109 0618, USA
Amyotroph Lateral Scler 9:141-8. 2008..Several polymorphic non-synonymous SNPs were also observed in patients and controls. These initial data suggest that mutations in VPS54 are not a major cause of ALS... - Sodium channel mutations in epilepsy and other neurological disordersMiriam H Meisler
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 0618, USA
J Clin Invest 115:2010-7. 2005..The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well... - Sodium channels and neurological disease: insights from Scn8a mutations in the mouseM H Meisler
Department of Human Genetics, University of Michigan, Ann Arbor 48109 0618, USA
Neuroscientist 7:136-45. 2001.... - Sodium channel gene family: epilepsy mutations, gene interactions and modifier effectsMiriam H Meisler
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 5618, USA
J Physiol 588:1841-8. 2010..Whole genome sequencing and exome sequencing in patients with epilepsy will soon make it possible to detect multiple variants and their interactions in the genomes of patients with seizure disorders... - Identification of epilepsy genes in human and mouseM H Meisler
Department of Human Genetics, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109 0618, USA
Annu Rev Genet 35:567-88. 2001..The development of pharmaceuticals directed towards specific epilepsy genotypes can be anticipated, and the introduction of patient mutations into the mouse genome will provide models for testing these targeted therapies... - Impaired motor function in mice with cell-specific knockout of sodium channel Scn8a (NaV1.6) in cerebellar purkinje neurons and granule cellsStephen I Levin
Dept of Human Genetics, University of Michigan, School of Medicine, Ann Arbor, MI 48109 0618, USA
J Neurophysiol 96:785-93. 2006..The loss of these channels leads to a decrease in Purkinje cell firing rates as well as a modification of the synaptic properties of afferent parallel fibers, with the ultimate consequence of disrupting motor behavior... - SCNM1, a putative RNA splicing factor that modifies disease severity in miceDavid A Buchner
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI 48109 0618, USA
Science 301:967-9. 2003..Our finding that genetic variation in a putative RNA splicing factor influences disease susceptibility in mice raises the possibility that a similar mechanism modifies the severity of human inherited disorders... - Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremorLisa M Sharkey
Department of Human Genetics, University of Michigan, 4812 Med Sci II, 1241 Catherine Street, Ann Arbor, MI 48109 5618, USA
Parkinsonism Relat Disord 15:321-3. 2009..SCN8A encodes the neuronal voltage gated sodium channel Na(v)1.6 that is widely expressed in the central nervous system. Several mutations of Scn8a in the mouse result in congenital postural tremor of the extremities and head... - De novo exon duplication in a new allele of mouse Glra1 (spasmodic)Katherine D Holland
Division of Neurology, Cincinnati Children s Hospital Medical Center, OH 45229 3039, and Department of Human Genetics, University of Michigan, Ann Arbor 48109 0618, USA
Genetics 174:2245-7. 2006..The mutant transcript results in premature protein truncation. A direct repeat of the pentamer GGGGC is present adjacent to the breakpoints and may have mediated the duplication event by a replication slippage mechanism... - Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancyJennifer A Kearney
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
Pediatr Neurol 34:116-20. 2006..Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides... - Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6)Stephen I Levin
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 0618, USA
Genesis 39:234-9. 2004..Conditional inactivation of the floxed allele will make it possible to circumvent the lethality that results from complete loss of Scn8a in order to investigate the physiologic role of NaV1.6 in subpopulations of neurons... - Multiple transcripts of sodium channel SCN8A (Na(V)1.6) with alternative 5'- and 3'-untranslated regions and initial characterization of the SCN8A promoterValerie L Drews
Department of Human Genetics, University of Michigan, 4708 Medical Science II, Ann Arbor, MI 48109 0618, USA
Genomics 85:245-57. 2005..Sequence comparison of human and mouse SCN8A identified 12 conserved noncoding elements whose effect on transcription was tested in transfected cells... - A targeted deleterious allele of the splicing factor SCNM1 in the mouseViive M Howell
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109 5618, USA
Genetics 180:1419-27. 2008..The phenotypes of the Scnm1Delta3-5 mutant confirm the role of this splice factor in processing the Scn8a(medJ) transcript and provide a new allele of greater severity for future studies... - Three ENU-induced neurological mutations in the pore loop of sodium channel Scn8a (Na(v)1.6) and a genetically linked retinal mutation, rd13David A Buchner
Department of Human Genetics, University of Michigan, Ann Arbor 48109 0618, USA
Mamm Genome 15:344-51. 2004..The new alleles of Scn8a will be valuable for analysis of sodium channel physiology and disease... - Mutations of voltage-gated sodium channels in movement disorders and epilepsyMiriam H Meisler
Department of Human Genetics, University of Michigan, Ann Arbor, 48109-0618, USA
Novartis Found Symp 241:72-81; discussion 82-6, 226-32. 2002..Advances in molecular methods coupled with genomic sequences from the Human Genome Project will permit identification of many new patient mutations and generation of animal models to dissect their physiological and cellular consequences... - Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6)Jennifer A Kearney
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor 48109, USA
Hum Mol Genet 11:2765-75. 2002..medJ mice provide a model for the physiological effects of sodium channel deficiency and the molecular mechanism of bigenic disease... - The ataxia3 mutation in the N-terminal cytoplasmic domain of sodium channel Na(v)1.6 disrupts intracellular traffickingLisa M Sharkey
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109 5618, USA
J Neurosci 29:2733-41. 2009..The data demonstrate that the cytoplasmic N-terminal domain of the sodium channel is required for anterograde transport from the Golgi complex to the plasma membrane... - Altered function of the SCN1A voltage-gated sodium channel leads to gamma-aminobutyric acid-ergic (GABAergic) interneuron abnormalitiesMelinda S Martin
Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA
J Biol Chem 285:9823-34. 2010..Decreased inhibition may be a common mechanism underlying clinically distinct SCN1A-derived disorders... - Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6Bryan T MacDonald
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0618, USA
Development 131:2543-52. 2004..These compensatory interactions between Dkk1 and Lrp6 demonstrate the importance of correctly balancing positive and negative regulation of Wnt signaling during mammalian development... - High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spotDavid A Buchner
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI 48109 0618, USA
Genomics 82:452-9. 2003..5 cM/Mb. The role of the modifier in other disorders in human and mouse can be tested with linked markers described here... - Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in miceLigia A Papale
Department of Human Genetics, Emory University, Atlanta, GA 30322, USA
Hum Mol Genet 18:1633-41. 2009..The abnormal EEG patterns in heterozygous mutant mice and the influence of genetic background on SWD make SCN8A an attractive candidate gene for common human absence epilepsy, a genetically complex disorder... - Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALSClement Y Chow
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Am J Hum Genet 84:85-8. 2009..Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases... - Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P? phosphatase FIG4Garth Nicholson
Department of Neurology, University of Sydney, ANZAC Institute, Concord Hospital, NSW 2139, Australia
Brain 134:1959-71. 2011..FIG4 mutations should be considered in Charcot-Marie-Tooth patients with these characteristics, especially if found in combination with sporadic or recessive inheritance, childhood onset and a phase of rapid progression... - VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouseNatsuko Jin
Department of Cell and Developmental Biology and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 2216, USA
EMBO J 27:3221-34. 2008..Moreover, these studies show that the association of Fab1 with the complex is essential for viability in the mouse... - Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2Cole J Ferguson
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 5618, USA
Hum Mol Genet 18:4868-78. 2009..These results establish a role for PI(3,5)P(2) in autophagy in the mammalian central nervous system (CNS) and demonstrate that mutations affecting PI(3,5)P(2) can contribute to inclusion body disease... - En1 and Wnt7a interact with Dkk1 during limb development in the mouseMaja Adamska
Department of Human Genetics, University of Michigan, Ann Arbor 48109 0618, USA
Dev Biol 272:134-44. 2004..The failure of Wnt7a inactivation to completely correct the limb defects of Dkk1d/dEn1-/- double mutants indicates that Wnt7a is not the only gene regulated by En1 during development of the mouse limb... - TSRC1, a widely expressed gene containing seven thrombospondin type I repeatsDavid A Buchner
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI 48109 0618, USA
Gene 307:23-30. 2003..Human TSRC1 is located on chromosome 1q21 within an 11.7 Mb segment of conserved synteny. TSRC1 and the closely linked gene ADAM15 appear to be derived by a chromosomal inversion that interrupted an ancestral ADAMTS gene... - Genetic interaction between Wnt7a and Lrp6 during patterning of dorsal and posterior structures of the mouse limbMaja Adamska
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109 0618, USA
Dev Dyn 233:368-72. 2005..The data are consistent with the view that Wnt7a acts through Lrp6 and the canonical Wnt signaling pathway during dorsal and posterior limb development in the mouse... - Sacred disease secrets revealed: the genetics of human epilepsyJulie Turnbull
The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada
Hum Mol Genet 14:2491-500. 2005..These, however, still account for a mere fraction of the genetic contribution to epilepsy. Exciting years are ahead, in which the genetics of this extremely common, and debilitating, neurological disorder will be solved... - Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouseThomas Schmitt-John
Developmental Biology and Molecular Pathology, Bielefeld University, Germany
Nat Genet 37:1213-5. 2005..Motoneuron survival and spermiogenesis are severely compromised in the wobbler mouse, indicating that Vps54 has an essential role in these processes... - Sacred disease secrets revealed: the genetics of human epilepsyJulie Turnbull
Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
Hum Mol Genet 14:2491-2500. 2005..These, however, still account for a mere fraction of the genetic contribution to epilepsy. Exciting years are ahead, in which the genetics of this extremely common, and debilitating, neurological disorder will be solved... - Motor disturbances in mice with deficiency of the sodium channel gene Scn8a show features of human dystoniaMelanie Hamann
Department of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universitat Berlin, Koserstrasse 20, 14195 Berlin, Germany
Exp Neurol 184:830-8. 2003..With the exception of muscle weakness, many of the features of the med(J) mouse are similar to human idiopathic dystonia... - Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsyKatherine D Holland
Division of Neurology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Neurosci Lett 433:65-70. 2008..This observation of a potentially pathogenic mutation of SCN3A (Nav1.3) indicates that this gene should be further evaluated for its contribution to childhood epilepsy... - Inactivation of sodium channel Scn8A (Na-sub(v)1.6) in Purkinje neurons impairs learning in Morris water maze and delay but not trace eyeblink classical conditioningDiana S Woodruff-Pak
Department of Psychology, Temple University, Philadelphia, PA 19122, USA
Behav Neurosci 120:229-40. 2006.... - Progressive loss of striatal neurons causes motor dysfunction in MND2 mutant mice and is not prevented by Bcl-2Silvia Rathke-Hartlieb
Developmental Biology and Molecular Pathology, University of Bielefeld, Bielefeld, D 33501, Germany
Exp Neurol 175:87-97. 2002..Thus, MND2 mutant mice may provide useful insights into molecular events underlying striatal cell death... - A hot spot for hotfoot mutations in the gene encoding the delta2 glutamate receptorYing Wang
Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Eur J Neurosci 17:1581-90. 2003..In addition, the frequent occurrence of in-frame deletions within the N-terminal domain in hotfoot mutants suggests the importance of this domain in the function of delta2 receptors... - Doubleridge, a mouse mutant with defective compaction of the apical ectodermal ridge and normal dorsal-ventral patterning of the limbMaja Adamska
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0618, USA
Dev Biol 255:350-62. 2003..doubleridge thus exhibits an unusual limb phenotype combining abnormal compaction of the AER with normal dorsal/ventral patterning... - Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degenerationXuebao Zhang
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA
Brain 131:1990-2001. 2008..This study represents the first documentation of the natural history of CMT4J. Physical obstruction of organelle trafficking by vacuoles is a potential novel cellular mechanism of neurodegeneration... - Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant miceJulie M Jones
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109 0618, USA
Nature 425:721-7. 2003..The neurodegeneration and juvenile lethality in mnd2 mice result from this defect in mitochondrial Omi protease...
Research Grants
- Gene interaction in development and diseaseMIRIAM MEISLER; Fiscal Year: 2009..We propose to extend this work to related genes and disorders, and to generate better animal models of the human disease in order to understand the pathogenic mechanism and provide an accurate model for testing therapeutic intervention. ..
- INSERTIONAL MUTANTS AND DEVELOPMENTMIRIAM MEISLER; Fiscal Year: 2003..The interaction between Scn8a and Scnm1 is a model for gene interactions that modify human susceptibility to inherited neurological disorders. ..
- Gene interaction in development and diseaseMiriam H Meisler; Fiscal Year: 2010....
- Functional Genetics of the Neuronal Sodium Channel Gene SCN8AMiriam H Meisler; Fiscal Year: 2010..This project will characterize the neurological and behavioral effects of specific changes in sodium channel genes, using mouse models of human mutations. ..
- Functional Genetics of the Neuronal Sodium Channel Gene SCN8AMIRIAM MEISLER; Fiscal Year: 2009..This project will characterize the neurological and behavioral effects of specific changes in sodium channel genes, using mouse models of human mutations. ..
- Functional Genetics of the Neuronal Sodium Channel Gene SCN8AMIRIAM MEISLER; Fiscal Year: 2007..This project will characterize the neurological and behavioral effects of specific changes in sodium channel genes, using mouse models of human mutations. ..
- MICHIGAN PREDOCTORAL TRAINING PROGRAM IN GENETICSMIRIAM MEISLER; Fiscal Year: 2007..The GTP is one of the oldest and largest NIH-supported training programs, and continues to be a vital component of graduate education and biomedical research at the University of Michigan. ..
- Gene interaction in development and diseaseMIRIAM MEISLER; Fiscal Year: 2007..Because of the high level of alternative splicing in the nervous system, variation in SCNM1 may be of particular significance for neurological disease. ..
- The neuronal sodium channel gene SCN8AMIRIAM MEISLER; Fiscal Year: 2006..This work will extend our knowledge of the physiological and cellular functions of SCN8A in the CNS and PNS and its role in neurological disease. ..
- NEUROMUSCULAR DISEASE GENE ENCODING A NEW SODIUM CHANNELMIRIAM MEISLER; Fiscal Year: 2000..Promoter function will also be assayed in transgenic mice. This work will provide thorough characterization of normal and mutated forms of a novel sodium channel and contribute to the diagnosis and treatment of neuromuscular disease. ..
- INSERTIONAL MUTANTS AND DEVELOPMENT IN TRANSGENIC MICEMIRIAM MEISLER; Fiscal Year: 1999..These projects will contribute to isolation of genes involved in craniofacial development, identification of new genetic disorders, and development of the human and mouse comparative genetic maps. ..
- GENETIC REGULATION OF MOUSE ENZYMESMIRIAM MEISLER; Fiscal Year: 1980..If we can understand how normal enzyme concentration is altered by mutation, the regulatory mechanisms responsible for maintenance of steady-state enzyme levels may be identified. ..
- INSERTIONAL MUTANTS AND DEVELOPMENT IN TRANSGENIC MICEMIRIAM MEISLER; Fiscal Year: 1993..Insertional mutation in transgenic mice provides a powerful system for the identification and genetic mapping of new functional elements in the mammalian genome, and for molecular characterization of these new genes...
- GENETIC REGULATION OF MOUSE ENZYMESMIRIAM MEISLER; Fiscal Year: 1991..These investigations will contribute to our understanding of the molecular basis of tissue-specific and hormonal regulation of mammalian gene expression...