Abstract
Knowing the mutational basis of a disease does not always explain the mechanism of pathogenesis, particularly when little is known about the disease-associated proteins themselves. This is very likely to be an ever-growing problem in the genomics era. The polyglutamine (polyQ) repeat disorders are an intriguing example of such a scientific dilemma. These human diseases presently include the spinocerebellar ataxia type 1 (SCA1, SCA2, SCA3, SCA6, SCA7), Huntington disease (HD), spinal and bulbar muscular atrophy (SBMA), and dentatorubropallidoluysian atrophy (DRPLA) (1). With the exception of SBMA and SCA6, due to the expansion of a polyQ in the androgen receptor and alpha1A voltage-dependent calcium channel, respectively, the wild-type function of the gene products are not understood. While the cloning of the polyQ genes has provided important genetic information, the biochemical mechanism responsible for each was not readily apparent. To gain insight into the molecular basis of polyQ-induced pathogenesis, investigators have turned to the development and characterization of disease models. Transgenic mice, in combination with cell culture models, have proven to be very useful tools for elucidating factors important for polyQ pathogenesis. This review focuses on those polyQ diseases for which informative studies have been undertaken using transgenic mice. For each disease, relevant information gleaned from other experimental approaches is also incorporated into the discussion.
Keywords: polyglutamine disease, transgenic mice, huntington, calcium channel, polyQ gene, SCA2, SBMA, protein misfolding, proteolysis
Current Genomics
Title: Expanding our Understanding of Polyglutamine Disease Through Transgenic Mice
Volume: 2 Issue: 1
Author(s): Jennifer D. Davidson and Harry T. Orr
Affiliation:
Keywords: polyglutamine disease, transgenic mice, huntington, calcium channel, polyQ gene, SCA2, SBMA, protein misfolding, proteolysis
Abstract: Knowing the mutational basis of a disease does not always explain the mechanism of pathogenesis, particularly when little is known about the disease-associated proteins themselves. This is very likely to be an ever-growing problem in the genomics era. The polyglutamine (polyQ) repeat disorders are an intriguing example of such a scientific dilemma. These human diseases presently include the spinocerebellar ataxia type 1 (SCA1, SCA2, SCA3, SCA6, SCA7), Huntington disease (HD), spinal and bulbar muscular atrophy (SBMA), and dentatorubropallidoluysian atrophy (DRPLA) (1). With the exception of SBMA and SCA6, due to the expansion of a polyQ in the androgen receptor and alpha1A voltage-dependent calcium channel, respectively, the wild-type function of the gene products are not understood. While the cloning of the polyQ genes has provided important genetic information, the biochemical mechanism responsible for each was not readily apparent. To gain insight into the molecular basis of polyQ-induced pathogenesis, investigators have turned to the development and characterization of disease models. Transgenic mice, in combination with cell culture models, have proven to be very useful tools for elucidating factors important for polyQ pathogenesis. This review focuses on those polyQ diseases for which informative studies have been undertaken using transgenic mice. For each disease, relevant information gleaned from other experimental approaches is also incorporated into the discussion.
Export Options
About this article
Cite this article as:
Davidson D. Jennifer and Orr T. Harry, Expanding our Understanding of Polyglutamine Disease Through Transgenic Mice, Current Genomics 2001; 2 (1) . https://dx.doi.org/10.2174/1389202013351183
DOI https://dx.doi.org/10.2174/1389202013351183 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Toll-Like Receptor Radical Cycle Pathway: A New Drug Target in Immune-Related Chronic Fatigue
CNS & Neurological Disorders - Drug Targets Mechanisms of ERK1/2 Regulation by Seven-Transmembrane-Domain Receptors
Current Pharmaceutical Design Does Pharmacological Therapy Still Play a Role in Preventing Sudden Death in Surgically Treated Tetralogy of Fallot?
Mini-Reviews in Medicinal Chemistry Amyloidogenesis of Natively Unfolded Proteins
Current Alzheimer Research Subject Index to Volume 10
Current Pharmaceutical Design H2O2 Signalling Pathway: A Possible Bridge between Insulin Receptor and Mitochondria
Current Neuropharmacology Is rTMS an Effective Therapeutic Strategy that Can Be Used to Treat Parkinson's Disease?
CNS & Neurological Disorders - Drug Targets Adenosine Dysfunction in Epilepsy and Associated Comorbidities
Current Drug Targets Neuropeptide Receptors in Intestinal Disease: Physiology and Therapeutic Potential
Current Pharmaceutical Design MDMA Toxicity and Pathological Consequences: A Review About Experimental Data and Autopsy Findings
Current Pharmaceutical Biotechnology The Neuroprotective Role of PEDF: Implication for the Therapy of Neurological Disorders
Current Molecular Medicine Physiological and Morphological Principles Underpinning Recruitment of the Cerebellar Reserve
CNS & Neurological Disorders - Drug Targets Future Challenges for Microsomal Transport Protein Inhibitors
Current Vascular Pharmacology The Immune System of Cancer Patients
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Involvement of Advanced Glycation End-products (AGEs) in Alzheimers Disease
Current Alzheimer Research Current Evidence and Potential Mechanisms of Therapeutic Action of PEDF in Cervical Cancer Treatment
Current Molecular Medicine Inflammation in Ischemic Stroke Subtypes
Current Pharmaceutical Design Perspectives and New Aspects of Metalloproteinases’ Inhibitors in the Therapy of CNS Disorders: From Chemistry to Medicine
Current Medicinal Chemistry Rho-ROCK Inhibitors for the Treatment of CNS Injury
Recent Patents on CNS Drug Discovery (Discontinued) Group I Metabotropic Glutamate Receptor Signalling and its Implication in Neurological Disease
CNS & Neurological Disorders - Drug Targets