Rat Genomics: Methods and Protocols (Methods in Molecular Biology, 597)

✍ Scribed by Ignacio Anegon (editor)

• Publisher: Humana
• Year: 2009
• Tongue: English
• Leaves: 460
• Category: Library

✦ Synopsis

Grown exponentially by the genomic revolution, the use of the rat as a model of choice for physiological studies continues in popularity and at a much greater depth of understanding. In Rat Genomics: Methods and Protocols, world-wide experts provide both practical information for researchers involved in genomic research in the rat along with a more contextual discussion about the usefulness of the rat in physiological or translational research in different organs and systems. The volume extensively covers topics including genome sequencing, quantitative trait loci mapping, and the identification of single nucleotide polymorphisms as well as the development of transgenic technologies such as nuclear cloning, lentiviral-mediated transgenesis, gene knock-down using RNA interference, gene knock-out by mutagenesis, and zinc finger nucleases plus exciting advances in the obtention of rat embryonic cell lines. As a volume in the highly successful Methods in Molecular Biology™ series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results.

Comprehensive and up-to-date, Rat Genomics: Methods and Protocols thoroughly covers the current techniques used in labs around the world and overviews the applications of the data obtained, making it certain to be useful to the scientific community as a key source of references and methods.

✦ Table of Contents

152432_Anegon_FM_O.pdf
Anegon_Ch01_O.pdf
Chapter 1
The Rat: A Model Used in Biomedical Research
1. .Introduction
2. .The Rat Toolbox
2.1. .Biochemistry, Nutrition, Pharmacology, and Physiology
2.2. .Molecular Genetic Tools
2.2.1. .Genetic Markers
2.2.2. .Genetic Sequence
2.2.3. .Other Genomic Tools
2.2.4. .Genetic Modifications
3. .Bioinformatic Tools
4. .Outlook
References
Anegon_Ch02_O.pdf
Chapter 2
Genetic Mapping and Positional Cloning
1. .Why Map Genes in the Rat?
2. .Successful Positional Cloning in the Rat
2.1. .Fine Mapping: The Success of Congenic, Subcongenic, Advanced Intercross Lines and Haplotype Mapping
2.2. .Recent Advances in Fine Mapping and Functional Tests of Candidate Genes
2.3. .Functional Tests of Candidate Genes
3. .Translation to Humans
4. .New Approaches in Rat Positional Cloning
5. .The Future of Genetic Mapping and Positional Cloning
References
Anegon_Ch03_O.pdf
Chapter 3
Sequencing of the Rat Genome and Databases
1. .Introduction
2. .Reference Genome
2.1. .Generation of the Reference Assembly
2.2. .Annotation of the Rat Genome
2.3. .Annotation of Other Elements on the Rat Genome
2.3.1. .SNPs
2.3.2. .CNVs
2.4. .Expression Data
2.5. .Comparative Genomics
3. .Major Databases and Bioinformatic Tools
3.1. .The National Center for Biotechnology Information
3.2. .Ensembl
3.3. .RGD
3.4. .UCSC
3.5. .Use Case 1
4. .Future Role of Genomic Sequence and Bioinformatics for the Rat
4.1. .Integrating Genomic Data
4.1.1. .Curation-Based Integration
4.1.2. .Programmatic Integration
4.2. .Use Case 2
References
Anegon_Ch04_O.pdf
Chapter 4
Design of Expression Cassettes for the Generation of Transgenic Animals (Including Insulators)
1. .Introduction
2. .The Overall Composition of the Vectors
3. .Use of Insulators
4. .Optimisation of the Transcribed Part
4.1. .5.'.-Untranslated Region
4.2. .Introns
4.3. .Codon Optimisation
4.4. .3.'.-Untranslated Region
4.5. .Simultaneous Expression of Several Cistrons
5. .Vectors to Inhibit the Expression of Endogenous Genes
5.1. .Gene Knockout
5.2. .Use of RNAi
5.3. .Use of Transdominant Negative Proteins
6. .Gene Targeting
7. .Conclusion
References
Anegon_Ch05_O.pdf
Chapter 5
Inducible and Conditional Promoter Systems to Generate Transgenic Animals
1. .Introduction
2. .Selection of Promoter for Controlling Gene Expression
3. .Gene Knockout
4. .RNAi
5. .Conditional and Inducible Transgene Expression
6. .Conditional Cell Knockout
7. .Conclusion
References
Anegon_Ch06_O.pdf
Chapter 6
Generation of Transgenic Rats by Microinjection of Short DNA Fragments
1. .Introduction
2. .Materials
2.1. .Male Vasectomy
2.2. .Superovulation and Pseudopregnant Females
2.3. .Zygote Preparations
2.4. .Injecting Zygotes – Microinjection
2.5. .Embryo Reimplantation
3. .Methods
3.1. .Male Vasectomy
3.2. .Superovulation and Pseudopregnant Females
3.3. .Zygote Preparations
3.4. .Injecting Zygotes – Microinjection
3.5. .Embryo Reimplantation
3.6. .Genotyping
4. .Notes
References
Anegon_Ch07_O.pdf
Chapter 7
Generation of Transgenic Rats Using YAC and BAC DNA Constructs
1. .Introduction
2. .Materials
2.1. .Preparation of YAC/BAC DNA for Microinjection
2.2. .Microinjection of YACs/BACs DNA
3. .Methods
3.1. .Preparation of YAC/BAC DNA for Microinjection
3.1.1. .Band Isolation of YACs/BACs from Agarose Plugs by PEGE (.see. Fig. .7.2.)
3.1.2. .Preparation of Isolated YACs/BACs from Agarose Gel (.see. Fig. .7.2.)
3.2. .Microinjection of YAC/BAC DNA into Rat Ova
3.2.1. .Making a Microinjection Pipette for Rat Ova (.see. Fig. .7.3.)
3.2.2. .Setting Up the Injection Pipette and Holding the Pipette Horizontally (.see. Fig7.4.)
3.2.3. .Improving Pipette Operations (.see. Fig. .7.5.)
4. Notes
References
Anegon_Ch08_O.pdf
Chapter 8
The Use of Lentiviral Vectors to Obtain Transgenic Rats
1. .Introduction
2. .Materials
2.1. .Materials for Lentiviral Vector Production
2.1.1. .Cell Culture
2.1.2. .Transfection
2.1.3. .Vector Collection and Concentration
2.1.4. .Vector Titration
2.1.5. .Safety Guidelines
2.2. .Materials and Animals for Production of Transgenic Rats
2.2.1. .Superovulation and Fertilized Embryo Collection
2.2.2. .Microinjection of One-Cell Embryos
2.2.3. .Transfer of Microinjected Embryos Into Recipient Females
3. .Methods
3.1. .Lentivirus Production Protocol
3.2. .Concentration of Recombinant Lentivirus
3.2.1. .Ultracentrifugation
3.2.2. .Chromatography
3.3. .Vector Titration
3.3.1. .“Biological Titer” Measurement by Cell Transduction and Real-Time Quantitative PCR
3.3.1.1. .Transduction of Target Hela Cells
3.3.1.2. .Real-Time Quantitative PCR
3.3.1.3. .Determination of the “Physical Titer” by Anti-p24 Immunoassay
3.3.1.4. .Use of Vector Stock
3.4. .Superovulation and Fertilized Embryo Collection
3.5. .Delivery of Lentiviruses to One-Cell Embryos
3.5.1. .Microinjection of Lentiviruses into the Perivitelline Space of Single-Cell Embryos
3.5.2. .Co-Incubation of Denuded One-Cell Embryos with Lentiviruses
3.6. .Transfer of Embryos into Recipient Females
3.7. .Genotyping Analysis of Founders
4. .Notes
References
Anegon_Ch09_O.pdf
Chapter 9
Generation of Transgenic Rats by Ooplasmic Injection of Sperm Cells Exposed to Exogenous DNA
1 Introduction
2. .Materials
2.1. .Media
2.1.1. .Modified-R1ECM
2.1.2. .Hepes-R1ECM
2.2. .Microtool
2.2.1. .Sperm Injecting Pipette
2.2.2. .Oocyte Holding Pipette
3. .Methods
3.1. .Oocyte Recovery
3.2. .Preparation of DNA-Bound Sperm
3.3. .ICSI Procedure
3.4. .Oviductal Transfer of ICSI Zygotes
4. .Notes
References
Anegon_Ch10_O.pdf
Chapter 10
Procedures for Somatic Cell Nuclear Transfer in the Rat
1. .Introduction
2. .Materials
2.1. .Oocytes Production
2.1.1. .Superovulation
2.1.2. .Oocytes Collection
2.2. .Nucleus Donor Cells Preparation
2.3. .Nuclear Transfer
2.4. .Activation of Embryos and Culture
2.5. .Embryo Transfer
3. .Methods
3.1. .Oocyte Production
3.1.1. .Superovulation
3.1.2. .Oocyte Collection and Preparation
3.2. .Nuclei Donor Cell Preparation
3.3. .Somatic Cell Nuclear Transfer
3.4. .Activation of Oocytes and Culture of Reconstructured Embryos
3.5. .Reimplantation of Reconstructed Embryos
4. .Notes
References
Anegon_Ch11_O.pdf
Chapter 11
ENU Mutagenesis to Generate Genetically Modified Rat Models
1. .Introduction
2. .Materials
2.1. .Animals and ENU Mutagenesis
2.2. .Library Generation and Genomic DNA Isolation
2.3. .Mutation Discovery
2.3.1. .Automated Resequencing
2.3.2. .The Yeast-Based Screening Assay
2.4. .Outcrossing
3. .Methods
3.1. .ENU Mutagenesis
3.1.1. .ENU Stock Solution Preparation
3.1.2. .ENU Administration to Male Rats
3.2. .Library Generation
3.3. .Mutation Discovery Protocols
3.3.1. .High-Throughput Resequencing
3.3.2. .Yeast-Based Screening Assay
3.4. .Outcrossing
4. .Notes
References
Anegon_Ch12_O.pdf
Chapter 12
Establishment of Embryonic Stem Cells from Rat Blastocysts
1. .Introduction
2. .Problems in Current Methods to Maintain Self-Renewal of ES Cells
3. .Establishment of Rat ES Cells by Reduction of Fetal Bovine Serum (FBS)
4. .Maintenance of Pluripotency and Self-Renewal by Signal Inhibitors
5. .Generation of Rat ES Cells by Combinations of Signal Inhibitors
6. .Future Prospects
References
Anegon_Ch13_O.pdf
Chapter 13
Derivation, Culture, and In vivo Developmental Capacity of Embryonic Cell Lines from Rat Blastocysts
1. .Introduction
2. .Materials
2.1. .Animals and Cells
2.2. .Culture Media and Materials
2.3. .Embryo Collection
3. .Methods
3.1. .Animals and Setup of Pairings
3.2. .Feeder Layers and Culture Media
3.3. .Embryo Collection
3.4. .Initial Culture
3.5. .Disaggregation of Blastocyst Outgrowths
3.6. .Long-Term Culture and Maintenance
3.7. .Assessment of In vivo Developmental Capacity
4. .Notes
References
Anegon_Ch14_O.pdf
Chapter 14
Interference RNA for In vivo Knock-Down of Gene Expression or Genome-Wide Screening Using shRNA
1. .Introduction
2. .Prerequisites for Successful Use of RNAi in Rat: Preliminary In vitro Demonstration of shRNA Effectiveness
2.1. .Lessons Learned from the RNAi Technology
2.2. .Design of shRNA Against Rat Genes – In vitro Validation of shRNA Specificity and Functionality
2.3. .shRNA Design and Target Selection
2.4. .Synthesis of shRNA Expression Plasmids for In vitro Validation Assays
2.5. .In vitro Functional Validation of shRNA Effectiveness
2.6. .In vitro Functional Validation of shRNA Specificity
3. .Shifting from In vitro Rat Gene Knock Down to In vivo Rat Gene Knock Down
3.1. .Lessons Learned for the Development of Transgenic Knock Down Mice Models
3.2. .First Proof of Concept of Knock Down Rat Models
3.3. .Bypassing the Limitations Associated to Random Integration: The Control of the Integration Site and the Number of Inserte
3.4. .Lessons Learned for the Development of Targeted Knock Down Mice Models
3.5. .Bypassing the Limitations Associated to Random Integration in Rat
4. .Future Development for In vivo Rat Gene Knock Down
4.1. .Lessons Learned from Development of Conditional Knock Down Mice Models
4.2. .Control of the shRNA Expression Using the Tetracycline System
4.3. .Control of the shRNA Expression Using the Cre/loxP System
4.3.1. .Insertion of a Transcription “Stop” Cassette in the Loop of the shRNA
4.3.2. .Insertion of a Transcription “Stop” Cassette Within the Polymerase III Promoter
4.3.3. .Insertion of a Transcription “Stop” Cassette in Between the Polymerase III Promoter and the shRNA Element
4.4. .Perspectives
for the Development of Conditional Knock Down Rat Models
4.4.1. .Control of shRNA Expression Using the Tetracycline System
4.4.2. .Control of the shRNA Expression Using the Cre/loxP System
5. .Conclusion
References
Anegon_Ch15_O.pdf
Chapter 15
Generation of Gene-Specific Mutated Rats Using Zinc-Finger Nucleases
1. .Introduction
2. .Materials
2.1. .Materials for Production and Gel Visualization of ZFN Messenger RNA
2.1.1. .ZFN mRNA Production
2.1.2. .Plasmid DNA Preparation for Microinjection
2.1.3. .Screening of ZFNs in Rat Cells
2.2. .Materials and Animals for Producing Gene Knockout Rats
2.2.1. .Superovulation and Fertilized Embryo Collection
2.2.2. .Microinjection of One-Cell Embryos
2.2.3. .Transfer of Microinjected Embryos into Recipient Females
2.3. .Materials for Assaying ZFN-Mediated Genome Editing
2.3.1. .Preparation of DNA from Rat Tissue
2.3.2. .Analysis of Rat Tissue for ZFN Modification
2.3.3. .Genotyping of ZFN-Modified Rats
3. .Methods
3.1. .In Vitro Transcription of ZFN mRNA
3.1.1. .Linearization of the Template DNA
3.1.2. .Capped In Vitro Transcription
3.1.3. .Polyadenosine-Tailing Reaction
3.1.4. .Purification and Gel Visualization of mRNA
3.1.5. .Preparation of Plasmid ZFN DNA for Microinjection
3.2. .Validating ZFN Activity Assay in Cultured Rat Cells
3.3. .Production of ZFN-Mediated Knockout Rats
3.3.1. .Selection of Rat Strain
3.3.2. .Superovulation and Fertilized Embryo Collection
3.3.3. .Delivery of ZFNs to One-Cell Embryos
3.3.4. .Transfer of Embryos into Recipient Females
3.4. .Analysis of Rat DNA for ZFN-Mediated Genome Editing
3.4.1. .Preparation of DNA from Rat Tissue
3.4.2. .Analysis of Rat Tissue for ZFN Modification
3.4.3. .Genotyping of ZFN-Modified Rats
3.5. .Obtaining Germline Transmission of ZFN-Modified Chromosomes
4. .Notes
References
Anegon_Ch16_O.pdf
Chapter 16
Application of Microarray-Based Analysis of Gene Expression in the Field of Toxicogenomics
1. .Introduction
2. .Materials
2.1. .Equipments
2.2. .Reagents
2.3. .User Manuals
3. .Methods
3.1. .Chemicals
3.2. .Animal Treatments
3.3. .RNA Isolation and Quality Control
3.4. .Microarray Platform
3.4.1. .Sample Labeling and Quality Control of Labeled aRNA
3.4.2. .aRNA Hybridization
3.4.3. .Scanning and Data Outputs
3.5. .Microarray Data Analysis
3.5.1. .Data Normalization
3.5.2. .Correlation, Cluster, and Principal Component Analyses
3.5.3. .Selection of Differentially Expressed Genes
3.6. .Validating Microarray Data
3.7. .Pathway and Functional Analysis
4. .Notes
References
Anegon_Ch17_O.pdf
Chapter 17
Generation of Congenic and Consomic Rat Strains
1. .Introduction
1.1. Definitions, Principles and Aims of Making Congenic and Consomic Rat Strains
1.2. .The Rat, a Leading Experimental Model for Studies of Human Diseases
1.3. .Use of Congenic Rats to Decipher Complex Genetic Traits
1.4. .Use of Consomic Rats to Decipher Complex Genetic Traits
2. .Material
2.1. .Zootechny Unit and Rats
2.2. .Genotyping
2.2.1. .DNA Extraction
2.2.2. .PCR Reaction for Agarose Gel Electrophoresis
2.2.3. .Agarose Gel Electrophoresis
2.2.4. .PCR Reaction for Capillary Electrophoresis (.see. .Note 8.)
2.2.5. .Capillary Electrophoresis
2.2.6. .SNPs Genotyping by qPCR
3. .Methods
3.1. .Genotyping
3.1.1. .Genotyping Using Microsatellite Markers
Microsatellite Marker Choice and Validation
Agarose Gel Electrophoresis
Capillary Electrophoresis
3.1.2. .Genotyping Using SNPs Markers
3.2. .Creation of Congenic Strains for a Whole Genomic Region and for Various Part of the Region Using the Speed Congenics Str
3.3. .Creation of Consomic Strains
3.4. .Construction of Sub-Strains from Congenic Strain or of Congenic Strain from Consomic Strain
3.5. .Quality Controls
4. .Notes
References
Anegon_Ch18_O.pdf
Chapter 18
Generation of Rat “Supersonic” Congenic/Conplastic Strains Using Superovulation and Embryo Transfer
1. .Introduction
2. .Materials
2.1. .Animals
2.2. .Superovulation and Embryo Manipulation
2.3. .Preparation of Foster-Mothers and Embryo Transfer
3. .Methods
3.1. .Animals
3.2. .Superovulation and Embryo Manipulation
3.3. .Preparation of Foster-Mothers and Embryo Transfer
3.4. .Genotyping
4. .Notes
References
Anegon_Ch19_O.pdf
Chapter 19
Analysis by Quantitative PCR of Zygosity in Genetically Modified Organisms
1. .Introduction
2. .Materials
3. .Genomic DNA Preparation
4. .Primer Design
5. .Real-Time PCR: Instruments and Reagents
6. .Methods
7. .DNA Preparation
8. .Primer Design
9. .Adjusting Parameters
10. .Real-Time PCR Procedure
11. .Calculation
12. .Notes
References
Anegon_Ch20_O.pdf
Chapter 20
A Restriction Enzyme-PCR-Based Technique to Determine Transgene Insertion Sites
1. .Introduction
2. .Materials
2.1. .Primers and Linkers
2.2. .DNA Extraction and Restriction Endonuclease Digestion
2.3. .PCR and Y-Linker Ligation
2.4. .Recovery of Amplification Products
3. .Methods
3.1. .Primer Design
3.2. .DNA Extraction and Restriction Endonuclease Digest
3.3. .First Round PCR
3.4. .Y-linker Ligation
3.5. .Second Round PCR
3.6. .Third Round PCR
3.7. .Recovery of Amplication Products
3.8. .Nucleotide Sequence Analysis of Recovered PCR products
3.9 .Troubleshooting
4. .Notes
References
Anegon_Ch21_O.pdf
Chapter 21
Cryopreservation and Orthotopic Transplantation of Rat Ovaries
1. .Introduction
2. .Materials
2.1. .Animals
2.2. .Buffer and Media for Cryopreservation and Thawing
2.3. .Equipment for Freezing, Storage and Thawing
2.4. .Equipment and Material for Ovary Preparation and Transplantation
3. .Methods
3.1. .Preparation of Donor Ovaries
3.2. .Cryopreservation and Thawing of Ovaries
3.2.1. .Cryopreservation
3.2.2. .Thawing
3.3. .Ovary Transplantation
3.4. .Vaginal Cytology
3.5. .Mating Regimen
4. .Notes
References
Anegon_Ch22_O.pdf
Chapter 22
Techniques for In Vitro and In Vivo Fertilization in the Rat
1. .Introduction
2. .Materials
2.1. .Collection of Epididymal Sperm
2.2. .Preparation of Recipient Females, and Vasectmized Males
2.3. .In Vitro Fertilization (IVF)
2.3.1. .Sperm Pre-incubation
2.3.2. .Superovulation
2.3.3. .Collection of Cumulus Oocyte Complexes (COCs) and Insemination (Co-culture with Sperm and COCs)
2.3.4. .Culture of Putative Zygotes
2.3.5. .Embryo Transfer of Zygotes (IVF embryos)
2.4. .In Vivo Fertilization: Intrauterine Insemination
2.4.1. .Sperm Freezing Medium
2.4.2. .Freezing of Epididymal Sperm
2.4.3. .Intrauterine Insemination
3. .Methods
3.1. .Collection of Epididymal Sperm
3.2. .Preparation of Recipient Females and Vasectmized Males
3.3. .IVF
3.3.1. .Sperm Pre-incubation
3.3.2. .Superovulation
3.3.3. .Collection of Cumulus Oocyte Complexes (COCs) and Insemination (Co-culture with Sperm and COCs)
3.3.4. .Culture of Putative Zygotes
3.3.5. .Embryo Transfer of Zygotes (IVF Embryos)
3.4. .In Vivo Fertilization: Intrauterine Insemination
3.4.1. .Freezing of Epididymal Sperm
3.4.2. .Intrauterine Insemination
4. .Notes
References
Anegon_Ch23_O.pdf
Chapter 23
Rat Strain Repositories
1. .Introduction
2. .Repositories
2.1. .The National Bio Resource Project for the Rat in Japan (NBRP-Rat)
2.2. .Rat Resource and Research Center
3. .Remarks
References
Anegon_Ch24_O.pdf
Chapter 24
Neurobehavioral Tests in Rat Models of Degenerative Brain Diseases
1. .Neurological Diseases in Rat Models
2. .The Problem of Standardized Behavioral Phenotyping
2.1. .Reasons for the Application of Automated High Throughput Screens in the Home Cage Environment
3. .Examples from Testing Transgenic Rats of Huntington’s and Spinocerebellar Ataxia Type 17
3.1. .A Proposed Test Battery for Repeated Testing and Screening of Rat Models
3.1.1. .SHIRPA1 Equivalent in Rats
Primary Screen in Transgenic Rat Models
Secondary Screen in Transgenic Rat Models
3.1.2. .Proposed Protocol for Accelerod Testing of Rats
3.1.3. .Proposed Protocol for Startle Response (SR) and Prepulse Inhibition (PPI) Testing of Rats
3.1.4. .Proposed Protocol for Social Interaction (SI) Test of Anxiety
4. .Future Developments: Automated Screens
4.1. .Technical Developments
4.2. .Present Experience Using Automated Phenotyping Technology
5. .Conclusion
References
Anegon_Ch25_O.pdf
Chapter 25
Rat Genomics Applied to Psychiatric Research
1. Introduction
2. .Rat Models Used in Psychiatric Research
3. Approaches Specific to Psychiatry-Related Traits
5. Transcriptomic and Proteomic Studies
7. Conclusion
References
Anegon_Ch26_O.pdf
Chapter 26
Genomics Studies of Immune-Mediated Diseases Using the BN–LEW Rat Model
1. .Introduction
2. .T Cell Subsets and Their Functions
3. .LEW and BN Rats Differ by Their Susceptibility to Immune-mediated Diseases
3.1. .Susceptibility of LEW and BN Rats to Th1-mediated Autoimmune Diseases: LEW Rats are Highly Susceptible While BN Rats are
3.2. .Susceptibility of LEW and BN Rats to Th2-mediated Autoimmune Diseases: BN Rats are Highly Susceptible Whereas LEW Rats ar
3.3. .LEW and BN Rats Exhibit Several Differences Concerning Their Immune System
4. .Linkage Analyses Using LEW.×.BN Intercross
5. .Genetic Dissection Using LEW/BN Congenic Lines
6. .Conclusions
References
Anegon_Ch27_O.pdf
Chapter 27
Rat Models of Cardiovascular Diseases
1. .Introduction
2. .Experimental Rat Models
2.1. .Experimental Models for Systemic Hypertension
2.1.1. .DOCA-Salt Hypertension
2.1.2. .NO Blockade
2.1.3. .Renovascular Hypertension
2.1.4. .Angiotensin II Infusion
2.2. .Experimental Models for Pulmonary Hypertension
2.2.1 .Monocrotaline
2.2.2. .Hypoxia
2.3. .Experimental Models for Myocardial Infarction
2.3.1. .Coronary Artery Ligation
2.4. .Experimental Models for Cardiac Hypertrophy
2.4.1. .Aortic Banding
2.4.2. .Aortocaval Shunt
2.4.3. .Isoproterenol
2.5. .Experimental Models for Stroke
2.5.1. .Middle Cerebral Artery Occlusion
3. .Genetic Rat Models
3.1. .Genetic Models for Systemic Hypertension
3.1.1. .Spontaneously Hypertensive Rats
3.1.2. .Milan Hypertensive Rats
3.1.3. .Lyon Hypertensive Rats
3.1.4. .New Zealand Hypertensive Rats
3.1.5. .Prague Hypertensive Rats
3.1.6. .Dahl Salt-Sensitive Rat
3.1.7. .San Juan Hypertensive Rats
3.1.8. .Sabra Rats
3.1.9. .Inherited Stress-Induced Arterial Hypertensive Rats
3.2. .Genetic Models for Pulmonary Hypertension
3.2.1. .Fawn-Hooded Rats
3.3. .Genetic Models for Heart Failure
3.3.1. .Spontaneously Hypertensive Heart Failure Rat
3.4. .Genetic Models for Stroke
3.4.1. .Stroke-Prone Spontaneously Hypertensive Rat
4. .Transgenic Models for Hypertension
4.1. .TGR(mREN2)27
4.2. .With Inducible Renin Expression
4.3. Human Renin/Human Angiotensinogen Double Transgenic Rats
4.4. .Other Transgenic Rat Models
References
Anegon_Ch28_O.pdf
Chapter 28
Use of Rat Genomics for Investigating the Metabolic Syndrome
1. .Introduction
2. .Recent Advances in Rat Genetics and Genomics
3. .Genetic Analyses of Complex Metabolic Traits in Rat Models
4. .The Spontaneously Hypertensive Rat and Derived Strains: A Model System for Genetic Analysis of the Metabolic Syndrome
4.1. .Recombinant Inbred Strains for the Analysis of Genes and Functional Networks Predisposing to Metabolic Syndrome
4.2. .Identification of Cd36 as a Gene Causing Defective Fatty Acid and Glucose Metabolism, and Increased Blood Pressure in the
5. .Conplastic Rats: The Role of Mitochondrial DNA in the Pathogenesis of Metabolic Syndrome
6. .Summary and Conclusions
References
Anegon_Ch29_O.pdf
Chapter 29
Genomic Research in Rat Models of Kidney Disease
1. .Introduction
2. .Pitfalls and Limitations in Investigating Renal Disease
3. .Genomic Investigation of Kidney Disease in the Rat
3.1. .Primary Renal Disease
3.1.1. .Glomerulosclerosis
Fawn-Hooded Rat
Munich Wistar Fromter (MWF)
Sabra Hypertension Prone (SBH/y)
Dahl Salt Sensitive (SS)
Buffalo/Mna Rat
Nephrotoxic Nephritis
3.1.2 IgA Nephropathy
3.2. .Secondary Renal Disease
3.2.1 Diabetic Nephropathy
3.2.1.1 Spontaneous Diabetes
Goto–Kakizaki rat
Zucker (fatty) Rat
T2DN
BioBreeding (BB) Rats
3.2.1.2 Induced Diabetes
Cohen Diabetic Rat
Streptozotocin (STZ) Rat
3.3. .Other Kidney Diseases
4. .Conclusions and Perspectives
References
Anegon_Ch30_O.pdf
Chapter 30
Cancer Research in Rat Models
1. .Introduction
2. .Toxicology, Carcinogenesis
3. .Hereditary Aspects
3.1. .Monogenic Cancers
3.1.1. .Colon Cancer (.Apc. Gene)
3.1.2. .Mammary Cancer (.Brca1. and .Brca2. Genes)
3.1.3. .Multiple Endocrine Neoplasia (.Cdkn1b. Gene)
3.1.4. .Renal Cancer (.Tsc2. and .Bdh. Genes)
3.1.5. .Teratoma
3.2. .Polygenic Cancers: Quantitative Trait Loci Analyses
4. .Cancer Somatic Genetics and Analysis of Rat Tumors
References
152432_Anegon_Index_O.pdf