Movement Disorders

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. mKv1.1^V408A/+: A Knockin Murine Model of EA1
  • 51.3. mKv1.1^−/−: A Knockout Murine Model of EA1
  • 51.4. rKv1.1^S309T/+: A Rat Model of EA1
  • 51.5. mKv1.1^ΔC/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