Medicine, Dentistry & Health Sciences Collected Works - Theses
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ItemAn exploratory study of allied health supervision models : acute and subacute care(University of Melbourne, 2010)
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ItemStudies on transgenic mice expressing an inducible Cre recombinase(University of Melbourne, 2010)Type 2 diabetes is characterised by muscle insulin resistance which is contributed to by defects in glucose storage. Glycogen synthase 1 (Gysl) is the rate-determining enzyme in the storage of glucose as glycogen in skeletal muscle and previous studies have associated insulin resistance in type 2 diabetic patients with defects in glycogen synthase activity. A Gy si homozygous global knockout mouse was recently generated and shown to lead to embryonic lethality. The aim of this study is to generate a tissue- specific mouse model of glycogen synthase deficiency using an inducible Cre-Lox system. We have previously generated mice expressing the inducible Cre, MerCreMer under the MLC1F promoter, which directs expression specifically to fast skeletal muscle. The construct used to generate Gysl-LoxP mice contains a PGK-Neo selection cassette used to identify transgene positive ES cells and our group and others have shown that the presence of the PGK-Neo selection cassette causes gene knockdown. To test the inducibility of our MerCreMer mice we have crossed them with the Gysl- Lox (Neo) line which functions as a reporter line. We have shown recombination levels of up to 90% in white quadriceps and no recombination in brain, heart and liver. From our Gysl-Lox (Neo) hemizygous lines we have shown at 10 weeks mRNA and protein levels were reduced by 50% in white quadriceps. We have recovered expression levels of Gysl to those of wildtype by removing Neo using the Flp/Frt system. We have crossed our MerCreMer line with the Gysl-Lox line to generate our inducible knockout animals. An induction regime of 5 days intraperitoneal injection with tamoxifen (1 mg/mouse/day) and a 14 day rest period has been carried out on these mice. Preliminary analysis has shown reduction in DNA and protein levels of Gysl in multiple tissues, including white quadriceps. Oral glucose tolerance tests have also been carried out on induced animals. Further numbers are needed to complete the analysis of the inducible knockout model. This will provide insights into the function of Gysl in skeletal muscle and peripheral insulin resistance, and improve on knowledge gained from the global Gysl knockout model.
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ItemAn exploratory study of the self-expressed reasons why older people and(University of Melbourne, 2010)
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ItemWhat Fathers have to say : the experience of Fathers in a neonatal intensive care unit(University of Melbourne, 2010)
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ItemSoluble epidermal growth factor receptor as a biomarker in colorectal cancer(University of Melbourne, 2010)
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ItemDoctors', nurses', and patients' perceptions of the emergency nurse practitioner role(University of Melbourne, 2009)
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ItemInteraction of iron, dopamine and ?-synuclein in a mouse model of Parkinson's disease(University of Melbourne, 2009)
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ItemInhibition of matrix metallopronteinase activity in the chick sclera and its effect on the development of myopia(University of Melbourne, 2009)
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ItemPost-traumatic stress disorder : the law and medicine(University of Melbourne, 2009)
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ItemDetermining differences in stroke unit care : Melbourne versus Trondheim(University of Melbourne, 2009)