
Movement Disorders
Genetics and Models
Description
Key Features
- Introduces the scientific foundations for modern movement disorders research
- Contributing authors are internationally known experts
- Completely revised with 20% new material
- Provides a comprehensive discussion of genetics for each type of movement disorder
- Covers Parkinson's disease, Huntington's disease, dystonia, tremors, and tics
Readership
Table of Contents
Section I. Scientific Foundations
- Chapter 1. Taxonomy and Clinical Features of Movement Disorders
- 1.1. Introduction
- 1.2. Parkinson Disease
- 1.3. Essential Tremor
- 1.4. Huntington Disease and Other Choreiform Disorders
- 1.5. Dystonia
- 1.6. Wilson Disease
- 1.7. Myoclonus
- 1.8. Gilles de la Tourette Syndrome
- 1.9. Drug-Induced Movement Disorders
- 1.10. Hemiballism
- 1.11. Summary
- Chapter 2. Modeling Disorders of Movement
- 2.1. Scientific Application of Animal Models
- 2.2. Choice of the Appropriate Animal Model
- 2.3. Experimental Approaches
- 2.4. Disorder-Specific Animal Models
- Chapter 3. New Transgenic Technologies
- 3.1. Genome Modification
- 3.2. Inducible Transgenes and Conditional Alleles
- 3.3. Applications of Transgenic Technology and Transgene Design
- 3.4. New Technologies: The Advent of Nucleases
- 3.5. Avoiding Experimental Snares in Animal Model Research
- 3.6. Future Prospects
- Chapter 4. Assessment of Movement Disorders in Rodents
- 4.1. Introduction
- 4.2. Basic Concepts of Animal Modeling
- 4.3. Specific Tests for Motor Abnormalities
- 4.4. Global Strategies for Assessing Movement Disorders
- 4.5. Suggested Test Batteries for Specific Movement Disorders
- 4.6. Summary
- Chapter 5. Drosophila
- 5.1. Introduction: A Historical Perspective on Flies and Genetic Disease Research
- 5.2. Basics of Genetic Analysis
- 5.3. Genes, Genome, and Homologies
- 5.4. Nervous System Organization
- 5.5. Detecting Movement Abnormalities
- 5.6. Genetic Tools of the Trade
- 5.7. Applications of the Drosophila Model in Movement Disorder Research
- 5.8. Prospects for the Future
- Chapter 6. Use of Caenorhabditis elegans to Model Human Movement Disorders
- 6.1. Caenorhabditis elegans: Why the Worm?
- 6.2. Caenorhabditis elegans Web-Based Resources
- 6.3. The C. elegans Nervous System
- 6.4. Detection of Movement Abnormalities
- 6.5. Tools of the Worm Trade
- 6.6. As the Worm Turns: Application of C. elegans to Movement Disorders Research
- 6.7. Drug Screening
- 6.8. Concluding Remarks
- Chapter 7. Zebrafish
- 7.1. Introduction
- 7.2. Why Zebrafish Models are Useful: Screens, In Vivo Imaging, and Genetic Tools
- 7.3. Zebrafish Genes, Cells, and Circuits Relevant to Studying Human Motor System Diseases
- 7.4. Zebrafish Genetic Methods: Knockouts and Transgenic Lines
- 7.5. Neurobehavioral Testing in Zebrafish
- 7.6. Chemical Screening
- 7.7. Conclusions
- Chapter 8. Techniques for Motor Assessment in Rodents
- 8.1. Introduction
- 8.2. Motor Coordination and Balance
- 8.3. Locomotor Activity
- 8.4. Fine Motor Skills
- 8.5. Akinesia and Muscular Strength
- 8.6. Conclusions
- Chapter 9. Induced Pluripotent Stem Cells (iPSCs) to Study and Treat Movement Disorders
- 9.1. Background
- 9.2. Modeling Movement Disorders Using iPSCs
- 9.3. Induced Pluripotent Stem Cells as a Platform for Cell Therapy and Drug Discovery
- 9.4. Conclusions
- Chapter 10. Neurophysiologic Assessment of Movement Disorders in Humans
- 10.1. Introduction
- 10.2. Assessment Methods
- 10.3. Movement Disorders
- 10.4. Recommendations and Conclusions
- 10.5. Conclusion
- Chapter 11. Neurophysiological and Optogenetic Assessment of Brain Networks Involved in Motor Control
- 11.1. Deep Brain Stimulation (DBS) as a Therapeutic Option for Parkinson Disease (PD)
- 11.2. Challenges and Opportunities in DBS Studies
- 11.3. The Expanding Toolkit Optogenetic Technologies
- 11.4. Experimental Optogenetic Technologies for Improving Existing DBS Practice
- 11.5. Conclusions
- Chapter 12. Functional Imaging to Study Movement Disorders
- 12.1. Introduction
- 12.2. Positron Emission Tomography
- 12.3. Single-Photon Emission Computed Tomography
- 12.4. Magnetic Resonance Imaging
- 12.5. Concluding Remarks
- Chapter 13. Human and Nonhuman Primate Neurophysiology to Understand the Pathophysiology of Movement Disorders
- 13.1. Introduction to the Basal Ganglia
- 13.2. Models of Basal Ganglia Function
- 13.3. Neurophysiologic Studies of the Basal Ganglia in PD
- 13.4. Dystonia
- 13.5. Summary
Section II. Parkinson Disease
- Chapter 14. The Phenotypic Spectrum of Parkinson Disease
- 14.1. Epidemiology of PD
- 14.2. Genetics of PD
- 14.3. Pathophysiology of PD
- 14.4. Clinical Features of PD
- 14.5. Summary
- Chapter 15. Genetics and Molecular Biology of Parkinson Disease
- 15.1. Introduction
- 15.2. Genetic Contribution to Parkinson Disease
- 15.3. Molecular Pathways in Parkinson Disease
- Chapter 16. Genotype–Phenotype Correlations in Parkinson Disease
- 16.1. Introduction
- 16.2. Dominant PD Genes
- 16.3. Recessive PD Genes
- 16.4. Additional Genes
- 16.5. Acid β-Glucosidase (GBA)
- 16.6. Limitations in Our Present Knowledge on Genotype–Phenotype Correlations
- 16.7. Subtypes of Parkinson Disease
- Chapter 17. From Man to Mouse: The MPTP Model of Parkinson Disease
- 17.1. Introduction
- 17.2. MPTP
- 17.3. Variations on the MPTP Mouse Model Theme
- 17.4. Non-MPTP Models of PD
- 17.5. Summary
- Chapter 18. Rodent Models of Autosomal Dominant Parkinson Disease
- 18.1. Introduction
- 18.2. Models of Parkinson Disease
- 18.3. SNCA
- 18.4. LRRK2 (PARK8)
- 18.5. UCHL1
- 18.6. Vacuolar Protein Sorting 35
- 18.7. Grb10-Interacting GYF Protein 2
- 18.8. HTRA2
- 18.9. Conclusions
- Chapter 19. Rodent Models of Autosomal Recessive Parkinson Disease
- 19.1. Autosomal Recessive PD
- 19.2. PARKIN
- 19.3. PINK1
- 19.4. DJ-1
- 19.5. Insights from Double and Triple Mutants
- 19.6. Conclusions
- Chapter 20. Drosophila Models of Parkinson Disease
- 20.1. Introduction
- 20.2. Modeling Parkinson Disease in Drosophila
- 20.3. Concluding Remarks
- Chapter 21. Primate Models of Complications Related to Parkinson Disease Treatment
- 21.1. Introduction
- 21.2. The Pathology of MPTP-Induced Parkinsonism
- 21.3. Levodopa-Induced Motor Complications
- 21.4. Successes, Failures, and Emerging Concepts on the Use of MPTP-NHPs in Translational Medicine
- 21.5. Nonmotor Complications of Advancing PD
- 21.6. Conclusion
- Chapter 22. Rodent Models of Treatment-Related Complications in Parkinson Disease
- 22.1. Introduction
- 22.2. Overview of the Main Molecular and Biochemical Correlates of Dyskinesia in Rodent Models
- 22.3. Challenges to Creating Rodent Models of Nonmotor Complications
- 22.4. Tasks for Cognitive and Psychiatric Dysfunction in Rodent Models of PD
- 22.5. Animal Models to Study Dopaminergic Modulation of ICDs
- 22.6. Animal Models to Study Dopaminergic Modulation of Cognitive Deficits
- 22.7. Concluding Remarks
- Chapter 23. Methods and Models of the Nonmotor Symptoms of Parkinson Disease
- 23.1. Introduction
- 23.2. Anxiety
- 23.3. Olfaction
- 23.4. Gastrointestinal
- 23.5. Sleep
- 23.6. Depression
- 23.7. Cognition
- 23.8. Summary
Section III. Dystonia
- Chapter 24. Dystonia: Phenotypes and Genetics
- 24.1. Introduction
- 24.2. Clinical Features
- 24.3. Primary Dystonia
- 24.4. Dystonia-Plus
- 24.5. Heredodegenerative Dystonia
- 24.6. Dystonia in Association with Other Neurogenetic Disorders
- 24.7. Conclusions
- Chapter 25. Murine Models of Caytaxin Deficiency
- 25.1. Phenotypic Characterization of the Genetically Dystonic Rat
- 25.2. Response of the Genetically Dystonic Rat to Pharmacological Agents
- 25.3. Neurochemical Analyses in the Genetically Dystonic Rat
- 25.4. Motoric Effects of Cerebellar Lesions in the Genetically Dystonic Rat
- 25.5. Olivocerebellar Neurophysiology in the Genetically Dystonic Rat
- 25.6. Genetics
- 25.7. Other Caytaxin Model Systems
- 25.8. Caytaxin
- 25.9. Relationship to Human Dystonia
- Chapter 26. Animal Models of Focal Dystonia
- 26.1. Introduction
- 26.2. Spasmodic Torticollis
- 26.3. Focal Hand Dystonia
- 26.4. Benign Essential Blepharospasm
- Chapter 27. Mouse Models of Dystonia
- 27.1. Introduction
- 27.2. Genetic Models of Dystonia
- 27.3. Drug-Induced Models of Dystonia
- 27.4. Summary and Conclusions
- Chapter 28. Rodent Models of Autosomal Dominant Primary Dystonia
- 28.1. Introduction
- 28.2. DYT1 Dystonia
- 28.3. Rodent Models of DYT11 Myoclonus-Dystonia
- 28.4. Rodent Model of DYT12 Dystonia
- 28.5. Rodent Model of DYT25 Dystonia
- 28.6. Conclusions from Rodent Models of Autosomal Dominant Primary Dystonia
- Chapter 29. Modeling Dystonia-Parkinsonism
- 29.1. Rapid-Onset Dystonia-Parkinsonism (DYT12)
- 29.2. The Na+/K+–ATpASE Pump
- 29.3. Animal Models of Rapid-Onset Dystonia-Parkinsonism
- 29.4. Alternating Hemiplegia of Childhood
- 29.5. Other Types of Dystonia with Signs of Dystonia and Parkinsonism
- 29.6. Conclusions
Section IV. Huntington Disease
- Chapter 30. Genetics of Huntington Disease (HD), HD-Like Disorders, and Other Choreiform Disorders
- 30.1. Autosomal Dominant Choreas
- 30.2. Autosomal Recessive Choreas
- 30.3. X-Linked Choreas (MCLeod Syndrome)
- 30.4. Conclusion
- Chapter 31. Murine Models of HD
- 31.1. Huntington Disease
- 31.2. The Use of Mice to Study Disease
- 31.3. Mouse Models of HD
- 31.4. Recommendations on the Use of HD Mouse Models in Therapeutics and Preclinical Studies
- 31.5. Conclusions
- Chapter 32. Use of Genetically Engineered Mice to Study the Biology of Huntingtin
- 32.1. Huntingtin Structure, Expression Pattern, and Protein Interactions
- 32.2. Huntingtin Function during Embryonic Development
- 32.3. Roles of Huntingtin in the Developing Brain
- 32.4. Neuroprotective Functions of Huntingtin
- 32.5. Roles of Huntingtin Structural Elements
- 32.6. Effects of Huntingtin in Peripheral Organ Systems
- 32.7. Conclusions
- Chapter 33. Modeling Huntington Disease in Yeast and Invertebrates
- 33.1. Introduction
- 33.2. Modeling HD in Yeast
- 33.3. Modeling HD in C. elegans
- 33.4. Modeling HD in Drosophila melanogaster
- 33.5. Conclusions and Future Directions
- Chapter 34. HDL2 Mouse
- 34.1. Introduction
- 34.2. The Contribution of Expanded Polyglutamine to HDL2 Pathogenesis
- 34.3. The Contribution of JPH3 Loss of Function to HDL2 Pathogenesis
- 34.4. The Contribution of RNA Toxicity to HDL2 Pathogenesis
- 34.5. Conclusions
- Chapter 35. Analysis of Nonmotor Features in Murine Models of Huntington Disease
- 35.1. Huntington Disease: The Importance of Nonmotor Disturbances
- 35.2. Huntington Disease Mouse Models Used for the Analysis of Huntington Disease Nonmotor Phenotypes
- 35.3. Depression and Anxiety in Huntington Disease Mouse Models
- 35.4. Cognitive Impairment in Huntington Disease Mouse Models
- 35.5. Metabolic Disturbances and Sleep Disturbances in Huntington Disease Mouse Models
- 35.6. Confounding Effects
- 35.7. Summary
Section V. Tremor
- Chapter 36. Essential Tremor
- 36.1. Introduction
- 36.2. Historical Perspective
- 36.3. Epidemiology
- 36.4. Clinical Features
- 36.5. Treatment
- 36.6. Pathophysiology and Pathology
- 36.7. Genetics
- Chapter 37. Use of the Harmaline and α1 Knockout Models to Identify Molecular Targets for Essential Tremor
- 37.1. Harmaline Model
- 37.2. The α1 KO Model
- 37.3. Attempts to Identify Drug Targets for Tremor Suppression
- 37.4. Survey of Other Potential Targets for ET Therapy
- 37.5. Concluding Remarks
- Chapter 38. Physiological and Behavioral Assessment of Tremor in Rodents
- 38.1. Tremor in Human Neuropathologies
- 38.2. Early Pharmacological Models of Tremor in Rodents: Cholinomimetics, Harmine, and Harmaline
- 38.3. Tremulous Jaw Movements in Rats: A Model of Parkinsonian Resting Tremor
- 38.4. Conclusions and Future Directions
- Chapter 39. Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation
- 39.1. Introduction
- 39.2. CGG Knockin Mouse Model of PM and FXTAS
- 39.3. CGG KI Mouse Behavioral Analyses
- 39.4. Future Directions
- 39.5. Conclusions
Section VI. Myoclonus
- Chapter 40. Myoclonus: Classification, Clinical Features, and Genetics
- 40.1. Introduction
- 40.2. Physiologic Classification
- 40.3. Clinical and Etiologic Classification
- Chapter 41. Mouse Model of Unverricht-Lundborg Disease
- 41.1. Introduction
- 41.2. Cystatin B-Deficient Mouse
- 41.3. Implications for Patient Care
- Chapter 42. Post-Hypoxic Myoclonus in Rodents
- 42.1. Historical Background
- 42.2. Procedures for Induction of Post-hypoxic Myoclonus in Rats
- 42.3. Behavioral Evaluation of Post-hypoxic Myoclonus in Rats
- 42.4. Pharmacological Studies for Validation of the Animal Model
- 42.5. Deficits in GABAergic and Serotonergic Activity in Post-hypoxic Myoclonus
- 42.6. Neurodegeneration Revealed by Histology Studies
- 42.7. Conclusions
- Chapter 43. Generating Mouse Models of Mitochondrial Disease
- 43.1. Introduction to Mitochondrial Disease Genetics and Mechanisms
- 43.2. Methods for Generating Mouse Models for Mitochondrial Diseases
- 43.3. Examples of Mouse Models of Nuclear-Encoded Mitochondrial Defects
- 43.4. Phenotypic Analysis of Mitochondrial Disease in Mouse Models
- 43.5. Concluding Remarks
Section VII. Tics
- Chapter 44. Tics and Tourette Syndrome: Phenomenology
- 44.1. Introduction
- 44.2. Phenomenology of Tics
- 44.3. Clinical Features of Tourette Syndrome
- 44.4. Neuropsychiatric Comorbidities
- 44.5. Differential Diagnosis and Pathophysiology of Tics and Tourette Syndrome
- Chapter 45. Genetics of Tourette Syndrome
- 45.1. Introduction
- 45.2. Familial Aggregation Studies
- 45.3. Heritability and Segregation Studies
- 45.4. Molecular Studies
- 45.5. Gene-Expression Studies
- 45.6. Relevance of Gene–Environment Interactions
- 45.7. Potential for Pathway Analyses of Genomic Data
- 45.8. Discussion and Future Directions
- Chapter 46. Neural Circuit Abnormalities in Tourette Syndrome
- 46.1. Clinical Characteristics as a Compass to Neuronal Substrates
- 46.2. Neuronal Correlates of Tic Generation and Tic Output—Findings from Magnetic Resonance Imaging
- 46.3. Neuronal Correlates of Tic Generation and Tic Output—Findings from Positron Emission Tomography
- 46.4. Resting State, Fine Motor Skills, and Neuronal Correlates of Voluntary Movements in Tourette Patients—Findings from Behavioral and Imaging Studies
- Chapter 47. Animal Models of Tourette Syndrome and Obsessive-Compulsive Disorder
- 47.1. TS Models
- 47.2. OCD Models
- 47.3. Conclusions
Section VIII. Paroxysmal Movement Disorders
- Chapter 48. Paroxysmal Movement Disorders: Clinical and Genetic Features
- 48.1. Introduction
- 48.2. Clinical Features
- 48.3. Genetics
- Chapter 49. Mouse Models of PNKD
- 49.1. PNKD
- 49.2. Mouse Models of PNKD
- 49.3. Mouse Models of PNKD—Phenotypes
- 49.4. Conclusions
- Chapter 50. Glut1 Deficiency (G1D)
- 50.1. Introduction
- 50.2. Disease Mechanisms
- 50.3. Disease Manifestations
- 50.4. Treatment
- 50.5. The G1D Mouse
- 50.6. Conclusions
- Chapter 51. Animal Models of Episodic Ataxia Type 1 (EA1)
- 51.1. Introduction
- 51.2. mKv1.1V408A/+: A Knockin Murine Model of EA1
- 51.3. mKv1.1−/−: A Knockout Murine Model of EA1
- 51.4. rKv1.1S309T/+: A Rat Model of EA1
- 51.5. mKv1.1ΔC/ΔC: A Megencephaly Mouse Mutant Displaying Ataxia and Seizures
- 51.6. Concluding Remarks
- Chapter 52. Mouse Models of Episodic Ataxia Type 2
- 52.1. Introduction
- 52.2. Cacna1a Mutations in Mice
- 52.3. Summary
Section IX. Tauopathies
- Chapter 53. Tauopathies: Classification, Clinical Features, and Genetics
- 53.1. Progressive Supranuclear Palsy
- 53.2. Corticobasal Degeneration
- 53.3. Genetics of PSP and CBD
- 53.4. Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17
- 53.5. Parkinsonism Dementia Complex of Guam
- 53.6. Postencephalic Parkinsonism
- 53.7. Globular Glial Tauopathy
- 53.8. Summary
- Chapter 54. Drosophila Models of Tauopathy
- 54.1. Introduction
- 54.2. The Double Life of Tau as a Physiologically Indispensable Neuronal Protein and a Neurotoxic Agent
- 54.3. Methodology: Using Drosophila to Study Tauopathy
- 54.4. Mechanisms of Tau Toxicity
- 54.5. Mechanisms Regulating Tau Toxicity
- 54.6. Neuroprotection against Tauopathy
- 54.7. Conclusion
- Chapter 55. Tauopathy Mouse Models
- 55.1. Introduction
- 55.2. The Tau Protein
- 55.3. Mouse Models Relying on Wild-type Human or Mouse Tau
- 55.4. Transgenic Mice Expressing Mutant Tau Transgenes
- 55.5. Transgenic Models of FTLD-Tau Splicing Mutations
- 55.6. Mouse Models of Glial Tau Pathology
- 55.7. Experimental Induction and Propagation “Seeding” Models
- Chapter 56. Tau Protein: Biology and Pathobiology
- 56.1. Introduction—A Brief History of Tau
- 56.2. Tau Function
- 56.3. Tau Toxicity
- 56.4. Tau Pathogenesis in Tauopathies
- 56.5. Tau Animal Models
- 56.6. Conclusion
Section X. Other Parkinsonian Syndromes: NBIA, MSA, PD + Spasticity, PD + Dystonia
- Chapter 57. Clinical Phenomenology and Genetics of Other Parkinsonian Syndromes Associated with Either Dystonia or Spasticity
- 57.1. Introduction
- 57.2. Atypical Parkinsonism—The Classical Parkinson-Plus Syndromes
- 57.3. Atypical Parkinsonism in Fragile X–Associated Tremor/Ataxia Syndrome
- 57.4. Dystonic Syndromes with Parkinsonism
- 57.5. Metal Accumulation Disorders
- 57.6. Other Dystonia-Parkinsonism Syndromes with Pyramidal Involvement and Often Other Complicating Features
- 57.7. Miscellaneous Conditions
- 57.8. Closing Remarks
- Chapter 58. Animal Models of Multiple-System Atrophy
- 58.1. Introduction
- 58.2. Clinical Presentation
- 58.3. General Considerations
- 58.4. Animal Models
- 58.5. Translational Aspects
- 58.6. Conclusions
- Chapter 59. Modeling PKAN in Mice and Flies
- 59.1. Introduction
- 59.2. Mouse Models
- 59.3. Drosophila Model for PKAN
- 59.4. Future Plans
- Chapter 60. Mouse Models of FA2H Deficiency
- 60.1. FA2H in the Nervous System
- 60.2. Fa2h Mutant Mice
- 60.3. Unanswered Questions
- Chapter 61. Mouse Models of Neuroaxonal Dystrophy Caused by PLA2G6 Gene Mutations
- 61.1. Introduction
- 61.2. Clinical Syndromes Associated with PLA2G6 Mutations
- 61.3. PLA2G6
- 61.4. Mouse Models
- 61.5. Summary and Future Directions
Section XI. Ataxias
- Chapter 62. Genetics and Clinical Features of Inherited Ataxias
- 62.1. Introduction
- 62.2. Autosomal Recessive Cerebellar Ataxia
- 62.3. Autosomal Dominant Ataxias
- 62.4. Spinocerebellar Ataxias
- Chapter 63. Animal Models of Spinocerebellar Ataxia Type 1
- 63.1. Introduction
- 63.2. Uncovering SCA1 Pathogenic Mechanisms via Animal Models
- 63.3. Concluding Remarks
- Chapter 64. Mouse Models of SCA3 and Other Polyglutamine Repeat Ataxias
- 64.1. SCA2 Mouse Models
- 64.2. SCA3 Mouse Models
- 64.3. SCA6 Mouse Models
- 64.4. SCA7 Mouse Models
- 64.5. SCA17 Mouse Models
- 64.6. DRPLA Mouse Models
- 64.7. Therapies for polyQ Diseases
- 64.8. Conclusions and Lesson Learned
- Chapter 65. Animal Models of Friedreich Ataxia
- 65.1. The FRDA Gene, Transcript and Frataxin
- 65.2. Animal Models
- Chapter 66. Ataxia-Telangiectasia and the Biology of Ataxia-Telangiectasia Mutated (ATM)
- 66.1. The Genetics and Biochemistry of AT
- 66.2. Modeling AT in the Mouse
- 66.3. The Neurophysiology of AT
- 66.4. ATM and the Impact of Nongenetic Factors
- 66.5. Conclusions
- Chapter 67. Autosomal Recessive Ataxias Due to Defects in DNA Repair
- 67.1. Introduction
- 67.2. Endogenous Sources of DNA Damage
- 67.3. DSB Repair
- 67.4. SSB Repair
- 67.5. Diseases Associated with Defects in SSB Repair
- 67.6. Tyrosyl DNA Phosphodiesterase 1
- 67.7. Spinocerebellar Ataxia with Axonal Neuropathy 1
- 67.8. Microcephaly, Infantile-Onset Seizures, and Developmental Delay (MCSZ)
- 67.9. X-Linked Mental Retardation (XLMR)
- 67.10. Ataxia Oculomotor Apraxia 1
- 67.11. Ataxia Oculomotor Apraxia 2
- 67.12. Neurodegeneration: Consequence of Repair Defects in the Nucleus, Mitochondria, or Both?
- 67.13. Animal Models and Future Research
- Chapter 68. Caenorhabditis elegans Models to Study the Molecular Biology of Ataxias
- 68.1. Introduction
- 68.2. The Use of C. elegans to Investigate the Molecular Basis of Human Ataxias
- 68.3. Final Remarks
Section XII. Hereditary Spastic Paraplegia
- Chapter 69. Hereditary Spastic Paraplegias: Genetics and Clinical Features
- 69.1. Introduction
- 69.2. Differential Diagnosis
- 69.3. Epidemiology and Genetics
- 69.4. Neuropathology
- 69.5. Treatments and Emerging Diagnostics
- 69.6. Conclusions
- Chapter 70. Mouse Models of Autosomal Dominant Spastic Paraplegia
- 70.1. Introduction
- 70.2. SPG4/Spastin KO Models
- 70.3. SPG31/REEP1 KO Model
- 70.4. SPG6/NIPA1 Transgenic Rats
- 70.5. SPG10/KIF5A Null and Conditional Mutant Mice
- 70.6. SPG17/BSCL2/Seipin Transgenic Mice
- 70.7. SPG13/HSPD1/HSP60 mutant mice
- 70.8. Conclusion and Future Directions
- Chapter 71. Murine Models of Autosomal Recessive Hereditary Spastic Paraplegia
- 71.1. Introduction
- 71.2. SPG5
- 71.3. SPG7
- 71.4. SPG20
- 71.5. SPG21
- 71.6. SPG26
- 71.7. SPG30
- 71.8. SPG39
- 71.9. SPG44
- 71.10. SPG47, SPG48, SPG50–52
- 71.11. ALS2
- 71.12. Conclusions
- Chapter 72. Modeling Hereditary Spastic Paraplegia (HSP) in Zebrafish
- 72.1. Spastin
- 72.2. Katanin
- 72.3. Protrudin
- 72.4. Strumpellin
- 72.5. Spatacsin, Spastizin, GBA2, and AT-1
- 72.6. Alsin
- 72.7. Atlastin and BMP Signaling
- 72.8. Conclusion
- Chapter 73. Drosophila Models of Hereditary Spastic Paraplegia
- 73.1. Introduction
- 73.2. Genes with Drosophila Mutants that Have Been Studied as Models of HSP
- 73.3. Genes with Drosophila Mutants Not Studied in the Context of HSP
- 73.4. Genes without Existing Drosophila Mutants
- 73.5. Conclusion
- Chapter 74. Caenorhabditis elegans Models of Hereditary Spastic Paraplegia
- 74.1. Use of Caenorhabditis elegans to Study HSP
- 74.2. HSP Caused by SPAST Mutations
- 74.3. HSP Caused by NIPA1 Mutations
- 74.4. HSP Caused by Kinesin Gene Mutations
- 74.5. Conclusions
- Chapter 75. Use of Arabidopsis to Model Hereditary Spastic Paraplegia and Other Movement Disorders
- 75.1. Introduction: Similarities between Human and Plant Cells
- 75.2. Similarities of Arabidopsis and Other Plants with Respect to Movement Disorder Pathways
- 75.3. Endogenous Plant Compounds May Protect against Movement Disorders
- 75.4. Summary
Section XIII. Restless Legs Syndrome
- Chapter 76. Clinical Phenotype and Genetics of Restless Legs Syndrome
- 76.1. Introduction
- 76.2. Epidemiology
- 76.3. Definition
- 76.4. The Clinical Phenotype
- 76.5. Therapy
- 76.6. Augmentation
- 76.7. Primary and Secondary RLS
- 76.8. RLS Mimics
- 76.9. RLS as a Genetic Disorder
- 76.10. Family Studies of RLS
- 76.11. Candidate Gene Association Studies
- 76.12. GenomeWide Association Studies
- 76.13. Following-up on GWAS
- 76.14. Future Directions in RLS Genetics
- Chapter 77. Combined D3 Receptor/Iron-Deficient Mouse Model
- 77.1. Combined D3 Receptor/Iron-Deficient Mouse Model
- 77.2. Iron Deficiency and Dopamine D3 Receptor Dysfunction as Possible Pathogenetic Factors
- 77.3. Rationale of a Combined Model of D3R and Iron Deficiency
- 77.4. Effects of Combined Iron and Dopamine D3 Receptor Deficiency on Different Aspects of Murine Behavior
- 77.5. Conclusion
- Chapter 78. Use of Drosophila to Study Restless Legs Syndrome
- 78.1. A Possible Genetic Basis for Restless Legs Syndrome
- 78.2. Drosophila as a Powerful Platform for Gene Function Analysis In vivo
- 78.3. Drosophila Is a Suitable Model to Investigate Locomotor and Sleep Phenotypes in RLS
- 78.4. Findings from a Reverse Genetic Model of RLS/Willis-Ekbom Disease in Flies
- 78.5. Potential Role for Dopamine and Iron in RLS as Inferred from the Fly Model
- 78.6. Drosophila as a Discovery Pipeline for Gene Networks in RLS and Sleep Regulation
- Chapter 79. The A11 Lesion/Iron Deprivation Animal Model of Restless Legs Syndrome
- 79.1. Background
- 79.2. Methods: Creating the Model
- 79.3. Methods—Evaluating the Phenotype
- 79.4. Methods: Immunohistochemistry to Confirm Lesioning Placement, Neurotransmitter Status, and Iron Status
- 79.5. Primary Results: Dopamine Cell Histology, Iron Analysis, and Behavioral Effects
- 79.6. Pharmacological Intervention Experiments
- 79.7. Determining the Effects of the Model on Spinal Cord Dopamine Receptors: Methods
- 79.8. Neurotransmitter and Receptor Results
- 79.9. Long-term Effects of Dopamine Agonist Treatment on Spinal Cord Receptors: Investigating Mechanism of Augmentation
- 79.10. Results of Long-term Treatment
- 79.11. Future Directions
- Chapter 80. Btbd9 Knockout Mice as a Model of Restless Legs Syndrome
- 80.1. Background on Restless Legs Syndrome
- 80.2. Biology of BTBD9
- 80.3. Btbd9 Knockout Mice
- 80.4. Discussion
- Chapter 1. Taxonomy and Clinical Features of Movement Disorders
Product details
- No. of pages: 1258
- Language: English
- Copyright: © Academic Press 2014
- Published: October 24, 2014
- Imprint: Academic Press
- eBook ISBN: 9780124055162