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.
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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 |
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