scholarly journals Mutational analysis of the androgen receptor (AR/Ar)-regulated transcriptome in mouse skeletal muscle models of Kennedy disease/spinal bulbar muscular atrophy

2015 ◽  
Author(s):  
K Mo
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Mutational Analysis ◽  
Muscular Atrophy ◽  
Mouse Skeletal Muscle ◽  
Spinal Bulbar Muscular Atrophy ◽  
Muscle Models

Structural and functional alterations in the androgen receptor in spinal bulbar muscular atrophy

2001 ◽  
Vol 29 (2) ◽  
pp. 222-227 ◽  
Author(s):  
I. J. McEwan
Keyword(s):  
Androgen Receptor ◽  
Spinocerebellar Ataxia ◽  
Muscular Atrophy ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Diverse Range ◽  
Disease States ◽  
Associated Proteins ◽  
Spinal Bulbar Muscular Atrophy ◽  
Clinical Conditions

The androgen receptor is a member of the nuclear receptor superfamily, and regulates gene expression in response to the steroid hormones testosterone and dihydrotestosterone. Mutations in the receptor have been correlated with a diverse range of clinical conditions, including androgen insensitivity, prostate cancer and spinal bulbar muscular atrophy, a neuromuscular degenerative condition. The latter is caused by expansion of a polyglutamine repeat within the N-terminal domain of the receptor. Thus the androgen receptor is one of a growing number of neurodegenerative disease-associated proteins, including huntingtin (Huntington's disease), ataxin-1 (spinocerebellar ataxia, type 1) and ataxin-3 (spinocerebellar ataxia, type 3), which show expansion of CAG triplet repeats. Although widely studied, the functions of huntingtin, ataxin-1 and ataxin-3 remain unknown. The androgen receptor, which has a well-recognized function in gene regulation, provides a unique opportunity to investigate the functional significance of poly(amino acid) repeats in normal and disease states.

Structural dynamics of the human androgen receptor: implications for prostate cancer and neurodegenerative disease

2006 ◽  
Vol 34 (6) ◽  
pp. 1098-1102 ◽  
Author(s):  
J. Duff ◽  
P. Davies ◽  
K. Watt ◽  
I.J. McEwan
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Structural Dynamics ◽  
Muscular Atrophy ◽  
Binding Domain ◽  
Genetic Changes ◽  
Kennedy’S Disease ◽  
Kennedy's Disease ◽  
Exon 1 ◽  
Spinal Bulbar Muscular Atrophy

The AR (androgen receptor) is a ligand-activated transcription factor that mediates the action of the steroids testosterone and dihydrotestosterone. Alterations in the AR gene result in a number of clinical disorders, including: androgen-insensitivity, which leads to disruption of male development; prostate cancer; and a neuromuscular degenerative condition termed spinal bulbar muscular atrophy or Kennedy's disease. The AR gene is X-linked and the protein is coded for by eight exons, giving rise to a C-terminal LBD (ligand-binding domain; exons 4–8), linked by a hinge region (exon 4) to a Zn-finger DBD (DNA-binding domain; exons 2 and 3) and a large structurally distinct NTD (N-terminal domain; exon 1). Identification and characterization of mutations found in prostate cancer and Kennedy's disease patients have revealed the importance of structural dynamics in the mechanisms of action of receptors. Recent results from our laboratory studying genetic changes in the LBD and the structurally flexible NTD will be discussed.

scholarly journals Disease Affects Bdnf Expression in Synaptic and Extrasynaptic Regions of Skeletal Muscle of Three SBMA Mouse Models

2019 ◽  
Vol 20 (6) ◽  
pp. 1314 ◽  
Author(s):  
Katherine Halievski ◽  
Samir Nath ◽  
Masahisa Katsuno ◽  
Hiroaki Adachi ◽  
Gen Sobue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mouse Models ◽  
Contractile Function ◽  
Muscular Atrophy ◽  
Synaptic Function ◽  
Bdnf Expression ◽  
Gene Dysregulation ◽  
Synaptic Region ◽  
Spinal Bulbar Muscular Atrophy

Spinal bulbar muscular atrophy (SBMA) is a slowly progressive, androgen-dependent neuromuscular disease in men that is characterized by both muscle and synaptic dysfunction. Because gene expression in muscle is heterogeneous, with synaptic myonuclei expressing genes that regulate synaptic function and extrasynaptic myonuclei expressing genes to regulate contractile function, we used quantitative PCR to compare gene expression in these two domains of muscle from three different mouse models of SBMA: the “97Q” model that ubiquitously expresses mutant human androgen receptor (AR), the 113Q knock-in (KI) model that expresses humanized mouse AR with an expanded glutamine tract, and the “myogenic” model that overexpresses wild-type rat AR only in skeletal muscle. We were particularly interested in neurotrophic factors because of their role in maintaining neuromuscular function via effects on both muscle and synaptic function, and their implicated role in SBMA. We confirmed previous reports of the enriched expression of select genes (e.g., the acetylcholine receptor) in the synaptic region of muscle, and are the first to report the synaptic enrichment of others (e.g., glial cell line-derived neurotrophic factor). Interestingly, all three models displayed comparably dysregulated expression of most genes examined in both the synaptic and extrasynaptic domains of muscle, with only modest differences between regions and models. These findings of comprehensive gene dysregulation in muscle support the emerging view that skeletal muscle may be a prime therapeutic target for restoring function of both muscles and motoneurons in SBMA.

scholarly journals Microarray Analysis of Gene Expression by Skeletal Muscle of Three Mouse Models of Kennedy Disease/Spinal Bulbar Muscular Atrophy

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12922 ◽  
Author(s):  
Kaiguo Mo ◽  
Zak Razak ◽  
Pengcheng Rao ◽  
Zhigang Yu ◽  
Hiroaki Adachi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mouse Models ◽  
Microarray Analysis ◽  
Muscular Atrophy ◽  
Spinal Bulbar Muscular Atrophy

scholarly journals Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy

2018 ◽  
Vol 24 (4) ◽  
pp. 427-437 ◽  
Author(s):  
Nisha M Badders ◽  
Ane Korff ◽  
Helen C Miranda ◽  
Pradeep K Vuppala ◽  
Rebecca B Smith ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Selective Modulation ◽  
Spinal Bulbar Muscular Atrophy

scholarly journals FUS is not dysregulated by the spinal bulbar muscular atrophy androgen receptor polyglutamine repeat expansion

2013 ◽  
Vol 34 (5) ◽  
pp. 1516.e17-1516.e19 ◽  
Author(s):  
Pietro Fratta ◽  
Bilal Malik ◽  
Anna Gray ◽  
Albert R. La Spada ◽  
Michael G. Hanna ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Repeat Expansion ◽  
Polyglutamine Repeat ◽  
Spinal Bulbar Muscular Atrophy

scholarly journals Autophagic and Proteasomal Mediated Removal of Mutant Androgen Receptor in Muscle Models of Spinal and Bulbar Muscular Atrophy

2019 ◽  
Vol 10 ◽  
Author(s):  
Maria Elena Cicardi ◽  
Riccardo Cristofani ◽  
Valeria Crippa ◽  
Veronica Ferrari ◽  
Barbara Tedesco ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Muscle Models

scholarly journals Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy

2008 ◽  
Vol 53 (5) ◽  
pp. 729-740 ◽  
Author(s):  
Douglas Ashley Monks ◽  
Pengcheng Rao ◽  
Kaiguo Mo ◽  
Jamie Ann Johansen ◽  
Gareth Lewis ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Spinal Bulbar Muscular Atrophy
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