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dc.contributor.authorNewbery, Helenen
dc.date.accessioned2018-05-22T12:46:16Z
dc.date.available2018-05-22T12:46:16Z
dc.date.issued2003
dc.identifier.urihttp://hdl.handle.net/1842/30572
dc.description.abstracten
dc.description.abstractMotor neuron disease, or amyotrophic lateral sclerosis (ALS), is a disorder characterised by progressive weakness and atrophy of skeletal muscles, caused by the selective loss of motor neurons. It occurs in both familial and sporadic forms. Although the genetic basis of the disease in a minority of cases has been identified, the precise molecular mechanism underlying the disease remains to be elucidated. There is a range of mouse mutants which model the disease. These mouse models, both classical and transgenic, have been particularly valuable in providing clues to the pathogenesis of the disease. One such mutant is wasted, in which the mice develop a progressive neuromuscular phenotype from 21 days of age. They deteriorate quickly, and die by 28 days. The genetic defect responsible for wasted is a 15kb deletion which leads to the abolition of the expression of eukaryotic elongation factor 1 A-2 (eEFlA-2). This is a tissue-specific isoform, apparently unique to mammals, of the more widely expressed eEFl A-l. In this PhD thesis I describe the further characterisation of wasted as a model for ALS, using immunohistochemistry to evaluate the similarities between the phenotype ofwasted mice and that ofALS patients. I have also screened the human gene, EEF1A2, for mutations in both familial and sporadic patients. Although there were polymorphisms within the gene which were also present in healthy controls, there were no mutations. It is thus unlikely that mutations in EEF1A2 are responsible for anything other than rare cases of ALS. I have designed and generated anti-peptide antibodies against eEFlA-l and eEFlA-2 which I have shown to be isoform-specific. These were used to study the expression of the two isoforms in mouse tissues. I have also shown that the African clawed frog, Xenopus laevis, has a developmentally-regulated, tissuespecific isoform homologous to eEFl A-2.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2018 Block 19en
dc.relation.isreferencedbyAlready catalogueden
dc.titleRole of eEF1A-2 in the pathogenesis of Motor Neurone Diseaseen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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