Cacnb4

Summary

Gene Symbol: Cacnb4
Description: calcium channel, voltage-dependent, beta 4 subunit
Alias: 3110038O15Rik, Cchb4, lethargic, CAB4, calcium channel voltage-dependent subunit beta 4, voltage-dependent L-type calcium channel subunit beta-4
Species: mouse

Top Publications

  1. pmc Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells
    Prakash Subramanyam
    Department of Physiology and Medical Physics, Division of Physiology, Medical University Innsbruck, Innsbruck, Austria
    Channels (Austin) 3:343-55. 2009
  2. ncbi Glial contribution to seizure: carbonic anhydrase activity in epileptic mammalian brain
    D Guillaume
    Laboratory of Biochemistry, University of Liege, Belgium
    Epilepsia 32:10-5. 1991
  3. ncbi Neuroanatomical substrates for paroxysmal dyskinesia in lethargic mice
    Rajiv Devanagondi
    Department of Neurology, Meyer Room 6 181, 600 North Wolfe Street, Johns Hopkins Hospital, Baltimore, MD 21287, and University of Tennessee, Memphis 38163, USA
    Neurobiol Dis 27:249-57. 2007
  4. pmc The light peak of the electroretinogram is dependent on voltage-gated calcium channels and antagonized by bestrophin (best-1)
    Lihua Y Marmorstein
    Department of Ophthalmology and Vision Science, University of Arizona, Tucson 85711, USA
    J Gen Physiol 127:577-89. 2006
  5. ncbi Requirement of voltage-gated calcium channel beta4 subunit for T lymphocyte functions
    Abdallah Badou
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 307:117-21. 2005
  6. ncbi Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer
    Sherry L Ball
    Research Service, Cleveland VA Medical Center, Cleveland, Ohio, USA
    Invest Ophthalmol Vis Sci 43:1595-603. 2002
  7. ncbi Pharmacological profiles of generalized absence seizures in lethargic, stargazer and gamma-hydroxybutyrate-treated model mice
    M Aizawa
    Department of Pharmacology, College of Pharmacy, Nihon University, Chiba, Japan
    Neurosci Res 29:17-25. 1997
  8. ncbi Ataxic mouse mutants and molecular mechanisms of absence epilepsy
    C F Fletcher
    MGL, ABL BRP, NCI Frederick Cancer Research and Development Center, Frederick, MD, USA
    Hum Mol Genet 8:1907-12. 1999
  9. ncbi Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami
    S J Caddick
    Department of Neurology, Medical College of Virginia, Richmond, Virginia 23298, USA
    J Neurophysiol 81:2066-74. 1999
  10. ncbi Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse
    D L Burgess
    Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 88:385-92. 1997

Research Grants

  1. Gene interaction in development and disease
    Miriam H Meisler; Fiscal Year: 2010
  2. INSERTIONAL MUTANTS AND DEVELOPMENT
    MIRIAM MEISLER; Fiscal Year: 2003
  3. Gene interaction in development and disease
    MIRIAM MEISLER; Fiscal Year: 2009
  4. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    Miriam H Meisler; Fiscal Year: 2010
  5. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    MIRIAM MEISLER; Fiscal Year: 2009
  6. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    MIRIAM MEISLER; Fiscal Year: 2007
  7. MICHIGAN PREDOCTORAL TRAINING PROGRAM IN GENETICS
    MIRIAM MEISLER; Fiscal Year: 2007
  8. Gene interaction in development and disease
    MIRIAM MEISLER; Fiscal Year: 2007
  9. The neuronal sodium channel gene SCN8A
    MIRIAM MEISLER; Fiscal Year: 2006
  10. INSERTIONAL MUTANTS AND DEVELOPMENT IN TRANSGENIC MICE
    MIRIAM MEISLER; Fiscal Year: 1999

Scientific Experts

  • MIRIAM MEISLER
  • J Barclay
  • R S Puranam
  • M W McEnery
  • GEORGE DOUGLAS LEIKAUF
  • Gerald J Obermair
  • Manabu Murakami
  • Daniel Burgess
  • D A Hosford
  • Abdallah Badou
  • Marc Freichel
  • Veit Flockerzi
  • Clotilde Ferrándiz-Huertas
  • Abir Tadmouri
  • Xingfu Xu
  • Y Wang
  • F H Lin
  • B Schlick
  • David W Cope
  • Prakash Subramanyam
  • Sabine Link
  • Stephanie Kuhn
  • Vsevolod Bodrikov
  • Renata Batista-Brito
  • F Lin
  • Rajiv Devanagondi
  • Simon Kaja
  • Lihua Y Marmorstein
  • Richard A Flavell
  • Didi Matza
  • Wajahat Z Mehal
  • S J Caddick
  • H A Jinnah
  • Ronald G Gregg
  • Lourdes Acosta
  • Neal S Peachey
  • Inseon Song
  • C F Fletcher
  • Hee Sup Shin
  • Sherry L Ball
  • Yi Zhang
  • Zubair Khan
  • C A Kozak
  • Yasuo Mori
  • Takafumi Miki
  • Shigeki Kiyonaka
  • Eloi Bahembera
  • Satoshi Akiyama
  • Karin Sadoul
  • Annie Andrieux
  • Michel Ronjat
  • Sylvie Gory-Fauré
  • Christophe Arnoult
  • Katell Fablet
  • Rafael Lujan
  • Michel De Waard
  • Seishiro Sawamura
  • Caroline Lambrecht
  • Veerle Janssens
  • Florian Lesage
  • Saadi Khochbin
  • Karin Pernet-Gallay
  • Mercedes Gil-Mínguez
  • Ricardo Dolmetsch
  • Matthieu Rousset
  • Sylvain Baulande
  • Maud Barbado
  • Robert E Oswald
  • William A Horne
  • Johanna B Holm
  • Mark D Terry
  • Yoon J Lee
  • J Qian
  • B E Flucher
  • S Wakana
  • Petra Weissgerber
  • Sabine Baumgartner
  • Martina Knirsch
  • Lukas Ruttiger
  • Gergely Orbán
  • David A Carter
  • Harald Winter
  • Timothy M Gould
  • Jutta Engel
  • Giuseppe Di Giovanni
  • Stephan Geley
  • Brigitte Held
  • Sylvia Kasperek
  • Sarah J Fyson
  • Walter A Kaufmann

Detail Information

Publications59

  1. pmc Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells
    Prakash Subramanyam
    Department of Physiology and Medical Physics, Division of Physiology, Medical University Innsbruck, Innsbruck, Austria
    Channels (Austin) 3:343-55. 2009
    ..The activity-dependent shuttling of beta(4b) into and out of the nucleus indicates a specific role of this beta subunit in neurons, in communicating the activity of calcium channels to the nucleus...
  2. ncbi Glial contribution to seizure: carbonic anhydrase activity in epileptic mammalian brain
    D Guillaume
    Laboratory of Biochemistry, University of Liege, Belgium
    Epilepsia 32:10-5. 1991
    ..The hypothesis of an adaptive glial mechanism, relating to the age-dependent decrease of seizure susceptibility in DBA/2 mice, is postulated...
  3. ncbi Neuroanatomical substrates for paroxysmal dyskinesia in lethargic mice
    Rajiv Devanagondi
    Department of Neurology, Meyer Room 6 181, 600 North Wolfe Street, Johns Hopkins Hospital, Baltimore, MD 21287, and University of Tennessee, Memphis 38163, USA
    Neurobiol Dis 27:249-57. 2007
    ..In the current studies, the anatomical basis for paroxysmal dyskinesias in lethargic mice was determined via histochemical methods sensitive to changes in regional brain activity followed by ..
  4. pmc The light peak of the electroretinogram is dependent on voltage-gated calcium channels and antagonized by bestrophin (best-1)
    Lihua Y Marmorstein
    Department of Ophthalmology and Vision Science, University of Arizona, Tucson 85711, USA
    J Gen Physiol 127:577-89. 2006
    ..Nimodipine diminished the LP, leading us to survey VDCC beta-subunit mutant mice. Lethargic mice, which harbor a loss of function mutation in the beta4 subunit of VDCCs, exhibited a significant shift in ..
  5. ncbi Requirement of voltage-gated calcium channel beta4 subunit for T lymphocyte functions
    Abdallah Badou
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 307:117-21. 2005
    ..Although Cav1 channels of lymphocytes retain their voltage dependency, T cell receptor stimulation dramatically increases channel opening, providing a new mechanism for calcium entry in lymphocytes...
  6. ncbi Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer
    Sherry L Ball
    Research Service, Cleveland VA Medical Center, Cleveland, Ohio, USA
    Invest Ophthalmol Vis Sci 43:1595-603. 2002
    ..The purpose of this study was to dentify which of the four beta subunits of VDCCs participates in the formation of this channel at the photoreceptor synapse and to determine how its absence affects visual processing...
  7. ncbi Pharmacological profiles of generalized absence seizures in lethargic, stargazer and gamma-hydroxybutyrate-treated model mice
    M Aizawa
    Department of Pharmacology, College of Pharmacy, Nihon University, Chiba, Japan
    Neurosci Res 29:17-25. 1997
    ..of generalized absence seizures in three mouse models: two mutant strains with spontaneous absence seizures, lethargic and stargazer, and ddY mice (GHB model) in which absence seizures were induced by administering gamma-..
  8. ncbi Ataxic mouse mutants and molecular mechanisms of absence epilepsy
    C F Fletcher
    MGL, ABL BRP, NCI Frederick Cancer Research and Development Center, Frederick, MD, USA
    Hum Mol Genet 8:1907-12. 1999
    ..Then, from the new wave of genetic and functional studies of these mutants we discuss their prospects for yielding insight into the molecular mechanisms of epilepsy...
  9. ncbi Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami
    S J Caddick
    Department of Neurology, Medical College of Virginia, Richmond, Virginia 23298, USA
    J Neurophysiol 81:2066-74. 1999
    Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami...
  10. ncbi Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse
    D L Burgess
    Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 88:385-92. 1997
    ..We used a positional candidate approach to determine that the ataxia and seizures in the lethargic (lh) mouse arise from mutation of the beta-subunit gene Cchb4 on mouse chromosome 2...
  11. ncbi beta subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain
    D L Burgess
    Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Neurosci 13:293-311. 1999
    ..The mouse mutant lethargic (lh) exhibits severe neurological defects due to a mutation that deletes the alpha1 subunit interaction domain ..
  12. pmc Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy
    Abir Tadmouri
    Unité INSERM U, Grenoble Institute of Neuroscience, Universite Joseph Fourier, La Tronche, France
    EMBO J 31:3730-44. 2012
    ..Here, we describe a novel signalling pathway in which the VGCC Cacnb4 subunit directly couples neuronal excitability to transcription...
  13. doi Regional expression and subcellular localization of the voltage-gated calcium channel β subunits in the developing mouse brain
    Clotilde Ferrándiz-Huertas
    Dept Ciencias Médicas, Instituto de Investigación en Discapacidades Neurológicas IDINE, Facultad de Medicina, Universidad Castilla La Mancha, Albacete, Spain
    J Neurochem 122:1095-107. 2012
    ..These results shed new light on the developmental regulation and subcellular localization of Ca(v) β subunits, and their possible role in pre- and post-synaptic transmission...
  14. ncbi Structures of the murine genes for the beta1- and beta4-subunits of the voltage-dependent calcium channel
    Manabu Murakami
    Department of Pharmacology, Akita University School of Medicine, 1 1 1, Hondou, Akita 010 8543, Japan
    J Mol Neurosci 21:13-21. 2003
    ..Furthermore, mRNA of these beta-subunits is strongly expressed in dorsal root ganglion neurons, which have many voltage-dependent calcium channels...
  15. ncbi Paroxysmal dyskinesias in the lethargic mouse mutant
    Zubair Khan
    Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA
    J Neurosci 22:8193-200. 2002
    b>Lethargic mutant mice carry a mutation in the CCHB4 gene, which encodes the beta4 subunit of voltage-regulated calcium channels...
  16. pmc Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1
    George D Leikauf
    Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219 3130, USA
    Am J Respir Crit Care Med 183:1499-509. 2011
    ..Because acute lung injury is a sporadic disease produced by heterogeneous precipitating factors, previous genetic analyses are mainly limited to candidate gene case-control studies...
  17. pmc Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons
    B Schlick
    Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria
    Neuroscience 167:786-98. 2010
    ..Developmental changes are likely determined by an intrinsic program and not regulated by changes in neuronal activity...
  18. ncbi Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons
    Yi Zhang
    Developmental Neurogenetics Laboratory, Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 22:6362-71. 2002
    ..1/alpha1A subunit), lethargic (lh; beta4 subunit), and stargazer (stg; gamma2 subunit) brain slices...
  19. ncbi Characterization of absence seizure-dependent cyclic AMP responsive element-and activator protein 1 DNA-binding activities in lethargic (lh/lh) mice
    K Ishige
    Department of Pharmacology, College of Pharmacy, Nihon University, Funabashi, Japan
    Neurosci Lett 262:53-6. 1999
    ..AMP responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in various brain regions of lethargic (lh/lh) mice, a genetic model of absence seizures...
  20. pmc Identification of epilepsy genes in human and mouse
    M 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...
  21. ncbi Gene mapping of SEZ group genes and determination of pentylenetetrazol susceptible quantitative trait loci in the mouse chromosome
    S Wakana
    Central Institute for Experimental Animals, Kawasaki, Japan
    Brain Res 857:286-90. 2000
    ..Since epilepsy is assumed to be a disease syndrome which is probably manifested by abnormal expression of multifocal genes, determination of the role of each chromosomal locus in the provocation of seizure activity is important...
  22. ncbi Presynaptic Ca(2+) influx at a mouse central synapse with Ca(2+) channel subunit mutations
    J Qian
    Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 20:163-70. 2000
    ..release at hippocampal Schaffer collateral synapses in both tottering (tg, alpha(1A) subunit) and lethargic (lh, beta(4) subunit) mutant mice...
  23. pmc Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function
    Abdallah Badou
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 103:15529-34. 2006
    ..These observations suggest that the Cav channels expressed by T cells have adopted novel regulation/gating mechanisms...
  24. ncbi Regional expression of L-type calcium channel subunits during cardiac development
    Lourdes Acosta
    Department of Experimental Biology, University of Jaen, Jaen, Spain
    Dev Dyn 230:131-6. 2004
    ..These findings suggest that beta subunits might play a major role in conferring calcium handling heterogeneity within the developing embryonic myocardium, while alpha1C subunits might contribute just transiently...
  25. ncbi Role of the alpha1G T-type calcium channel in spontaneous absence seizures in mutant mice
    Inseon Song
    Center for Calcium and Learning, Korea Institute of Science and Technology, Cheongryang, Seoul, 136 791, Korea
    J Neurosci 24:5249-57. 2004
    ..e., lethargic (beta4(lh/lh)), tottering (alpha1A(tg/tg)), or stargazer (gamma2(stg/stg))...
  26. pmc Reciprocal interactions regulate targeting of calcium channel beta subunits and membrane expression of alpha1 subunits in cultured hippocampal neurons
    Gerald J Obermair
    Department of Physiology and Medical Physics, Innsbruck Medical University, Austria
    J Biol Chem 285:5776-91. 2010
    ....
  27. pmc Enhanced tonic GABAA inhibition in typical absence epilepsy
    David W Cope
    School of Biosciences, Cardiff University, Cardiff, UK
    Nat Med 15:1392-8. 2009
    ..These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic importance and highlight potential therapeutic targets for the treatment of absence epilepsy...
  28. ncbi Ba2+ currents in inner and outer hair cells of mice lacking the voltage-dependent Ca2+ channel subunits beta3 or beta4
    Stephanie Kuhn
    Institute of Physiology II and Department of Otorhinolaryngology, Molecular Neurobiology, University of Tubingen, Tübingen Hearing Research Centre, Tubingen, Germany
    Channels (Austin) 3:366-76. 2009
    ..These results indicate that neither Ca(V)beta3 nor Ca(V)beta4 are indispensable for hair cell Ca(2+) currents but contribute to the overall current properties...
  29. pmc Diversity and developmental expression of L-type calcium channel beta2 proteins and their influence on calcium current in murine heart
    Sabine Link
    Experimentelle und Klinische Pharmakologie und Toxikologie, Universitat des Saarlandes, 66421 Homburg, Germany
    J Biol Chem 284:30129-37. 2009
    ....
  30. pmc NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its catalytic activity and neurite outgrowth
    Vsevolod Bodrikov
    Zentrum für Molekulare Neurobiologie, Universitat Hamburg, 20246 Hamburg, Germany
    J Cell Biol 182:1185-200. 2008
    ..Thus, we reveal a novel function for a cell adhesion molecule in coordination of cell behavior with intracellular phosphatase activity...
  31. pmc Gene expression in cortical interneuron precursors is prescient of their mature function
    Renata Batista-Brito
    Smilow Neuroscience Program and the Department of Cell Biology, Smilow Research Building, New York University Medical Center, 522 First Avenue, New York, NY 10016, USA
    Cereb Cortex 18:2306-17. 2008
    ..Moreover, our work has revealed that many of the genes expressed in cortical interneuron precursors have been independently linked to neurological disorders in both mice and humans...
  32. ncbi Redundancy of Cav2.1 channel accessory subunits in transmitter release at the mouse neuromuscular junction
    Simon Kaja
    Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
    Brain Res 1143:92-101. 2007
    ..Ducky, lethargic and stargazer are mutant mice that lack functional alpha(2)delta-2, beta(4) and gamma(2) accessory Ca(v) channel ..
  33. pmc The Ca2+ channel beta4c subunit interacts with heterochromatin protein 1 via a PXVXL binding motif
    Xingfu Xu
    Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 286:9677-87. 2011
    ..An NMR-based two-site docking model of β4c in complex with dimerized CSD is presented. Possible roles for the interaction are discussed...
  34. ncbi Single gene defects in mice: the role of voltage-dependent calcium channels in absence models
    D L Burgess
    Department of Neurology, Baylor College of Medicine, Houston, TX 77303, USA
    Epilepsy Res 36:111-22. 1999
    ..The tottering (tg) locus encodes the calcium channel alpha1 subunit gene Cacna1a, lethargic (lh) encodes the beta subunit gene Cacnb4, and stargazer (stg) encodes the gamma subunit gene Cacng2...
  35. ncbi Mutations of calcium channel beta subunit genes in mice
    D Freise
    Institut fur Pharmakologie und Toxikologie, Universitat des Saarlandes, Homburg, Germany
    Biol Chem 380:897-902. 1999
    ..Here we summarize the phenotype of mice deficient in the beta1 subunit, the beta3 subunit or the beta4 subunit, respectively...
  36. ncbi Genetic mapping of the peripheral sodium channel genes, Scn9a and Scn10a, in the mouse
    C A Kozak
    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 4, Room 329, Bethesda, Maryland 20892 0460, USA
    Mamm Genome 7:787-8. 1996
  37. ncbi The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products
    R Berger
    Institute of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Isreal
    Genome Res 6:361-70. 1996
    ..These findings suggest that there may be more human transcripts than currently recognized. The possible involvement of the new growing family of Tmpo proteins in nuclear architecture and cell cycle control is discussed...
  38. ncbi Increased number of GABAB receptors in the lethargic (lh/lh) mouse model of absence epilepsy
    F H Lin
    Department of Medicine Neurology, Duke University, Durham, NC
    Brain Res 608:101-6. 1993
    This study begins to explore possible mechanisms underlying the role of GABAB receptors in absence seizures in lethargic (lh/lh) mice...
  39. ncbi GABAB receptor-mediated effects in synaptosomes of lethargic (lh/lh) mice
    F H Lin
    Department of Medicine Neurology, Duke University, Durham, North Carolina, USA
    J Neurochem 65:2087-95. 1995
    ..we have shown a significant increase in number of GABAB receptor binding sites in neocortex and thalamus of lethargic (lh/lh) mice, a mutant strain exhibiting absence seizures...
  40. ncbi Characterization of the antiabsence effects of SCH 50911, a GABA-B receptor antagonist, in the lethargic mouse, gamma-hydroxybutyrate, and pentylenetetrazole models
    D A Hosford
    Department of Medicine Neurology, Duke University, Duke University Medical Center, Durham, North Carolina, USA
    J Pharmacol Exp Ther 274:1399-403. 1995
    ..In this study we measured the antiabsence effects of SCH 50911 in three animal models: the lethargic (lh/lh) mutant mouse, which has spontaneous absence seizures; and two rat models in which absence seizures were ..
  41. ncbi Genetic mapping of the mouse genes encoding the voltage-sensitive calcium channel subunits
    H Chin
    Laboratory of Neurochemistry, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genomics 28:592-5. 1995
    ..The alpha 1, beta 2, and beta 4 subunit genes, termed Cchna1, Cchb2, and Cchb4, are located at different sites on proximal Chr 2, while the beta 3 subunit gene Cchb3 maps to Chr 15 near Wnt1...
  42. ncbi Neural network of structures in which GABAB receptors regulate absence seizures in the lethargic (lh/lh) mouse model
    D A Hosford
    Department of Medicine Neurology, Duke University, Durham, North Carolina, USA
    J Neurosci 15:7367-76. 1995
    In previous work we have shown that GABAB receptors are required for expression of absence seizures in the lethargic (lh/lh) mouse model; that lh/lh mice have increased numbers of GABAB binding sites compared to nonepileptic littermates (..
  43. ncbi Chronological studies of peripheral motor nerve conduction in "lethargic" mice
    J M Herring
    Electromyogr Clin Neurophysiol 21:121-34. 1981
  44. ncbi Histo-pathologic observations of the nervous and lymphoid tissues of "lethargic" mutant mice
    H C Dung
    Tex Rep Biol Med 30:23-39. 1972
  45. ncbi The role of GABAB receptor activation in absence seizures of lethargic (lh/lh) mice
    D A Hosford
    Department of Medicine, Duke University, Durham, NC
    Science 257:398-401. 1992
    b>Lethargic (lh/lh) mice, which function as an animal model of absence seizures, have spontaneous seizures that have behavioral and electrographic features and anticonvulsant sensitivity similar to those of human absence seizures...
  46. ncbi The role of GABAB mechanisms in animal models of absence seizures
    S J Caddick
    Division of Neurology, Duke University Medical Center, Durham, NC, USA
    Mol Neurobiol 13:23-32. 1996
    ..The current evidence and interpretations of this work are presented here...
  47. ncbi Deficiency in the thymus-dependent immunity in "lethargic" mutant mice
    H C Dung
    Transplantation 23:39-43. 1977
    T cell function of "lethargic" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests...
  48. ncbi Organization, sequence, chromosomal localization, and promoter identification of the mouse orphan nuclear receptor Nurr1 gene
    S O Castillo
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 1766, USA
    Genomics 41:250-7. 1997
    ..These data help to explain the different response characteristics of two closely related early response genes, Nurr1 and Nur77...
  49. ncbi Mouse models of spike-wave epilepsy
    J Barclay
    Department of Paediatrics, The Rayne Institute, University College London Medical School, England, UK
    Epilepsia 40:17-22. 1999
    ..The lethargic mouse has been shown to be due to mutations in the gene encoding another calcium channel subunit, beta4...
  50. ncbi Age-related relationship between mRNA expression of GABA(B) receptors and calcium channel beta4 subunits in cacnb4lh mice
    F Lin
    Departments of Medicine Neurology and Neurobiology, Duke University and Veterans Administration Medical Centers, Durham, NC 27705, USA
    Brain Res Mol Brain Res 71:131-5. 1999
    ..In this study, we examined the relationship between Cacnb4 and GABA(B) receptor mRNA expression in brains from Cacnb4lh homozygotes and (+/+) controls...
  51. ncbi Glutamate decarboxylase isoforms in thalamic nuclei in lethargic mouse model of absence seizures
    F H Lin
    Departments of Medicine Neurology and Neurobiology, Epilepsy Research Laboratory, Duke University and Veterans Administration Medical Centers, Bldg 16, Rm 38, 508 Fulton St, Durham, NC, 27705, USA
    Brain Res Mol Brain Res 71:127-30. 1999
    ..These data suggest that GABA-synthesis is maintained or increased in NRT neurons in the Cacnb4lh mouse model...
  52. ncbi Decreased (45)Ca(2)(+) uptake in P/Q-type calcium channels in homozygous lethargic (Cacnb4lh) mice is associated with increased beta3 and decreased beta4 calcium channel subunit mRNA expression
    F Lin
    Department of Medicine Neurology, Duke University Medical Center, Durham, NC 27705, USA
    Brain Res Mol Brain Res 71:1-10. 1999
    The mutated gene in the lethargic (Cacnb4lh) mouse model of absence seizures encodes the beta4 subunit of voltage-gated calcium channels (VGCCs), leading to decreased mRNA expression of a beta4 subunit that is truncated and cannot bind ..
  53. ncbi Seizure disorders in mutant mice: relevance to human epilepsies
    R S Puranam
    Department of Medicine Neurology, Box 3676, Duke University Medical Center, 401 Bryan Research Building, Research Drive, Durham, North Carolina, 27710, USA
    Curr Opin Neurobiol 9:281-7. 1999
    ....
  54. ncbi Altered expression and assembly of N-type calcium channel alpha1B and beta subunits in epileptic lethargic (lh/lh) mouse
    M W McEnery
    Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106 4970, USA
    J Biol Chem 273:21435-8. 1998
    ..The focus of this study is the expression and assembly of alpha1B and beta isoforms in the epileptic mouse, lethargic (lh/lh), a mutant anticipated to produce a truncated beta4 subunit (Burgess, D. L., Jones, J. M., Meisler, M. H...
  55. pmc Divergent expression of alpha1-protease inhibitor genes in mouse and human
    J Tardiff
    Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Campus Box 347, Boulder, CO 80309, USA
    Nucleic Acids Res 26:3794-9. 1998
    ..This difference between the species appears to result from an absence of a functional macrophage-specific promoter in mice...
  56. ncbi Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic
    A Escayg
    Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, 48109 0618, USA
    Genomics 50:14-22. 1998
    The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal myoclonus, and absence epilepsy due to a loss-of-function mutation in the beta4 subunit of the voltage-gated calcium channel...
  57. ncbi Ion channel mutations in mouse models of inherited neurological disease
    M H Meisler
    Department of Human Genetics, University of Michigan, Ann Arbor 48109 0618, USA
    Ann Med 29:569-74. 1997
    ..have been identified by positional cloning of the spontaneous mouse mutants motor endplate disease, tottering, lethargic and weaver...
  58. ncbi Mapping of the human Ca2+ channel beta 4 subunit to 2q22-23 and its expression in developing mouse
    R Betz
    Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
    Mamm Genome 9:310-1. 1998
  59. ncbi A study of the increased serum level of IgG1 in 'lethargic' mice combined with a depressed thymus-dependent lymphoid system
    H C Dung
    J Immunogenet 4:287-93. 1977
    In a series of recent studies on 'lethargic' mice, a neurological mutation of the mouse, significant abnormalities were discovered in the thymus and its dependent regions in the lymph nodes and spleen...

Research Grants66

  1. Gene interaction in development and disease
    Miriam H Meisler; Fiscal Year: 2010
    ....
  2. INSERTIONAL MUTANTS AND DEVELOPMENT
    MIRIAM MEISLER; Fiscal Year: 2003
    ..The interaction between Scn8a and Scnm1 is a model for gene interactions that modify human susceptibility to inherited neurological disorders. ..
  3. Gene interaction in development and disease
    MIRIAM 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. ..
  4. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    Miriam 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. ..
  5. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    MIRIAM 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. ..
  6. Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
    MIRIAM 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. ..
  7. MICHIGAN PREDOCTORAL TRAINING PROGRAM IN GENETICS
    MIRIAM 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. ..
  8. Gene interaction in development and disease
    MIRIAM 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. ..
  9. The neuronal sodium channel gene SCN8A
    MIRIAM 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. ..
  10. INSERTIONAL MUTANTS AND DEVELOPMENT IN TRANSGENIC MICE
    MIRIAM 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. ..
  11. GENETIC REGULATION OF MOUSE ENZYMES
    MIRIAM 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...
  12. INSERTIONAL MUTANTS AND DEVELOPMENT IN TRANSGENIC MICE
    MIRIAM 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...
  13. GENETIC REGULATION OF MOUSE ENZYMES
    MIRIAM 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. ..
  14. NEUROMUSCULAR DISEASE GENE ENCODING A NEW SODIUM CHANNEL
    MIRIAM 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. ..
  15. Growth Factor Protection in Acute Lung Injury
    GEORGE LEIKAUF; Fiscal Year: 2009
    ..The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, ..
  16. Role of Metalloproteinases in Mucin Overproduction in COPD
    GEORGE DOUGLAS LEIKAUF; Fiscal Year: 2010
    ....
  17. Molecular Biology of Calcuim Channel Gamma Subunits
    Daniel Burgess; Fiscal Year: 2006
    ....
  18. Characterization of N-type Ca channels in growth cones
    Maureen McEnery; Fiscal Year: 2005
    ....