title: Absence of disturbed axonal transport in spinal and bulbar muscular atrophy.
abstract: Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is a late-onset motor neuron disease (MND) caused by an abnormal expansion of the CAG repeat in the androgen receptor (AR) gene on the X-chromosome, encoding a polyglutamine (poly-Q) sequence in the protein product. Mutant poly-Q-expanded AR protein is widely expressed but leads to selective lower motoneuron death. Although the mechanisms that underlie SBMA remain unclear, defective axonal transport has been implicated in MND and other forms of poly-Q disease. Transcriptional dysregulation may also be involved in poly-Q repeat pathology. We therefore examined axonal transport in a mouse model of SBMA recapitulating many aspects of the human disease. We found no difference in the expression levels of motor and the microtubule-associated protein tau, in the spinal cord and sciatic nerve of wild-type (WT) and SBMA mice at various stages of disease progression. Furthermore, we found no alteration in binding properties of motor proteins and tau to microtubules. Moreover, analysis of axonal transport rates both in cultured primary motoneurons in vitro and in vivo in the sciatic nerve of adult WT and mutant SBMA mice demonstrated no overt axonal transport deficits in these systems. Our results therefore indicate that unlike other motoneuron and poly-Q diseases, axonal transport deficits do not play a significant role in the pathogenesis of SBMA.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Bilal
authors.initials: B
authors.lastname: Malik
authors.forename: Niranjanan
authors.initials: N
authors.lastname: Nirmalananthan
authors.forename: Lynsey G
authors.initials: LG
authors.lastname: Bilsland
authors.forename: Albert R
authors.initials: AR
authors.lastname: La Spada
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gallo
authors.forename: Linda
authors.initials: L
authors.lastname: Greensmith
mesh_terms: D000818:Animals; D001370:Axonal Transport; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016875:tau Proteins