Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice

Dion, Patrick A.; Shanmugam, Vijayalakshmi; Gaspar, Cláudia; Messaed, Christiane; Meijer, Inge A.; Toulouse, André; Laganière, Janet; Roussel, Julie; Rochefort, Daniel; Laganiere, Simon; Allen, Carol A.; Karpati, George; Bouchard, Jean‐Pierre; Brais, Bernard; Rouleau, Guy

doi:10.1016/j.nbd.2004.09.021

Cited by 48 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present findings concur with data on homozygote OPMD patients [5] underlining the previously unsuspected neurodegenerative component, also described in transgenic mice [18], although the primary origin of OPMD symptoms was thought to be related to damage of muscular tissue.…”

Section: Discussionsupporting

confidence: 92%

Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy

Dubbioso¹,

Moretta

Manganelli³

et al. 2011

J Neurol

View full text Add to dashboard Cite

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder caused by a small expansion of a short polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). It presents with adult onset of progressive eyelid drooping, swallowing difficulties and proximal limb weakness, usually without involvement of central nervous system (CNS). However, cognitive decline with relevant behavioural and psychological symptoms has been recently described in homozygous patients. In this study, we performed for the first time an extensive neuropsychological and neuropsychiatric evaluation on 11 OPMD heterozygote patients. We found that they were less efficient than a matched control sample on several tests, particularly those tapping executive functions. Moreover, the presence of negative correlation between GCN expansion size and some neuropsychological scores raises the issue that CNS involvement might be linked to the genetic defect, being worse in patients with larger expansion. Our results might be consistent with the toxic gain-of-function theory in the pathogenesis of OPMD and hint at a possible direct role of PABPN1 in the CNS also in heterozygote patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy

Dubbioso¹,

Moretta

Manganelli³

et al. 2011

J Neurol

View full text Add to dashboard Cite

show abstract

“…In support of this hypothesis, transgenic mice expressing an expanded GCG repeat in the Pabpn1 gene showed ubiquitinated Pabpn1 positive intranuclear inclusions in brain neurons and Purkinje cells (15). It is possible that similar pathological changes occur in the human brain.…”

Section: Discussionmentioning

confidence: 75%

Oculopharyngeal Muscular Dystrophy Associated with Dementia

et al. 2011

View full text Add to dashboard Cite

We report genetically confirmed heterozygote oculopharyngeal muscular dystrophy (OPMD) accompanied by dementia, suggesting a possible causal association between OPMD and dementia. The proband first noticed bilateral ptosis, dysphagia, and proximal dominant muscle weakness in the lower extremities at age 53. Ten years later, she was found to have dementia with a score of 10/30 on the mini-mental state examination (MMSE). On PABPN1 gene analysis, the GCN repeat was expanded 17 times in one allele. In addition, the proband's younger brother exhibited myopathy and dementia. To our knowledge, this is the first report of genetically confirmed heterozygote OPMD associated with dementia.

show abstract

“…Oculopharyngeal muscular dystrophy (OPMD) is a protein aggregate disorder caused by the abnormal expansion of a polyalanine tract within the coding region of poly (A) binding protein nuclear 1 (PABPN1). Recently, animal models for OPMD were generated by transgenic expression of mutated poly-A binding nuclear protein 1 PABPN1 [35][36][37] using three different promoters. Mice expressing mutated PABPN1 under the CAG promoter, which drives a strong and ubiquitous expression, had a severe neuropathic phenotype and minimal myopathic changes [35].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, animal models for OPMD were generated by transgenic expression of mutated poly-A binding nuclear protein 1 PABPN1 [35][36][37] using three different promoters. Mice expressing mutated PABPN1 under the CAG promoter, which drives a strong and ubiquitous expression, had a severe neuropathic phenotype and minimal myopathic changes [35]. Mice expressing mutant PABPN1 under the PABPN1 promoter showed an exclusively myopathic phenotype and developed muscle weakness [36].…”

Section: Discussionmentioning

confidence: 99%

Non-pathogenic protein aggregates in skeletal muscle in MLF1 transgenic mice

Jiang

et al. 2008

Journal of the Neurological Sciences

View full text Add to dashboard Cite

Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice

Cited by 48 publications

References 34 publications

Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy

Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy

Oculopharyngeal Muscular Dystrophy Associated with Dementia

Non-pathogenic protein aggregates in skeletal muscle in MLF1 transgenic mice

Contact Info

Product

Resources

About