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Title: A study of the novel gene Clwd and its role in the pathology of the mouse mutant wasted
Author: O'Donoghue, J. E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Abstract:
Wasted (wst) is a recessive spontaneous mutation in the mouse resulting in a complex phenotype incorporating neuromuscular wasting and atrophy of the organs of the immune system. The genetic lesion in wasted mice is a 15.8 Kb deletion on mouse chromosome 2. Here I will describe the study of a novel gene in close proximity to the wasted deletion. This new gene Clwd (Close to the Wasted Deletion) is a small 1.2 Kb gene which appears (from EST data) to be ubiquitously expressed. It has several alternative splice forms and a short conserved upstream Open Reading Frame or uORF. The protein it encodes is 115 amino acids long with no striking homology to other proteins in the database. These features have been confirmed using RT-PCR and by generating and using an anti-peptide antibody to Clwd. Immunocytochemistry shows Clwd to be associated with the nuclear membrane. Upon the application of RNA interference (RNAi) to silence the Clwd gene transiently in mammalian cell culture, cells lacking Clwd display dysregulation of the cell cycle with cells appearing to have disrupted nuclei and slowed growth. As a result of this study I believe it unlikely that Clwd is responsible for the immunological phenotype of wasted mice. There is no difference in Clwd mRNA or protein expression between wasted and wild type controls. A transgenic project has been carried out in the lab whereby mice were injected with a BAC containing the whole genomic region surrounding the deletion, and a BAC containing the whole genomic region, but with eEF1A2 knocked out. Analysis of these animals suggest the pathology of wasted is due solely to the lack of eEF1A2. I will describe some preliminary studies to assess the importance of eEF1A2 expression in the dendritic cells of the immune system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.660268  DOI: Not available
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