Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice.

Disease Models & Mechanisms
Anna L GrayBilal Malik

Abstract

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's Disease, is a late-onset X-linked progressive neuromuscular disease, which predominantly affects males. The pathological hallmarks of the disease are selective loss of spinal and bulbar motor neurons, accompanied by weakness, atrophy and fasciculations of bulbar and limb muscles. SBMA is caused by a CAG repeat expansion in the gene that encodes the androgen receptor (AR) protein. Disease manifestation is androgen dependent and results principally from a toxic gain of AR function. There are currently no effective treatments for this debilitating disease. It is important to understand the course of the disease in order to target therapeutics to key pathological stages. This is especially relevant in disorders such as SBMA, for which disease can be identified before symptom onset, through family history and genetic testing. To fully characterise the role of muscle in SBMA, we undertook a longitudinal physiological and histological characterisation of disease progression in the AR100 mouse model of SBMA. Our results show that the disease first manifests in skeletal muscle, before any motor neuron degeneration, which only occurs in late-stage disease. These findings ...Continue Reading

References

Jun 1, 1997·Journal of Inherited Metabolic Disease·K H Fischbeck
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shuyuan YehMin-Chi Hung
Oct 22, 2002·The Journal of Biological Chemistry·Jessica L Walcott, Diane E Merry
May 11, 2004·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Masahisa KatsunoGen Sobue
May 21, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erica S Chevalier-LarsenDiane E Merry
Jan 22, 2005·Brain : a Journal of Neurology·Hiroaki AdachiGen Sobue
Apr 20, 2006·Brain : a Journal of Neurology·Naoki AtsutaGen Sobue
Sep 15, 2007·Journal of the Neurological Sciences·Gianni SorarùCorrado Angelini
Oct 20, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Isabella PalazzoloAngelo Poletti
Jun 19, 2008·Journal of Alzheimer's Disease : JAD·Andrew P Lieberman, Diane M Robins
Oct 23, 2009·Brain : a Journal of Neurology·Lindsay E RhodesKenneth H Fischbeck
Feb 15, 2011·Human Molecular Genetics·Bilal MalikLinda Greensmith
May 18, 2012·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Bernadett KalmarLinda Greensmith
May 7, 2013·Acta Neuropathologica·Adriana MalenaLodovica Vergani
Jun 6, 2014·Brain : a Journal of Neurology·Karli MontagueLinda Greensmith
Aug 12, 2014·Nature Neuroscience·Constanza J CortesAlbert R La Spada
Sep 24, 2014·Endocrine Development·Ralf Werner, Paul-Martin Holterhus
May 6, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Youfen XuCynthia L Jordan
Feb 9, 2017·Biochemistry·Adewale AdegbuyiroJustin Legleiter
May 17, 2018·Archives of Endocrinology and Metabolism·Rafael Loch BatistaBerenice Bilharinho de Mendonca
Jul 15, 2018·Journal of Neurology·Marianthi Breza, Georgios Koutsis

❮ Previous
Next ❯

Citations

Jun 10, 2020·International Journal of Molecular Sciences·Fiona LimanaqiFrancesco Fornai
Feb 9, 2021·Frontiers in Neurology·Elina MillereViktorija Kenina

❮ Previous
Next ❯

Methods Mentioned

BETA
force measurement
biopsy
force measurements
transgenic
PCR

Software Mentioned

SPSS
Picoscope

Related Concepts

Related Feeds

Researcher Network:CZI Neurodegeneration Challenge

The Neurodegeneration Challenge Network aims to provide funding for and to bring together researchers studying neurodegenerative diseases. Find the latest research from the NDCN grantees here.