Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.643194
Title: Disruption of the Ren-1d gene
Author: Clark, Allan F.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Abstract:
Physiologically, JG cells are the mot important sites of renin expression since they are the only cells known to convert prorenin to the active enzyme, renin, and to secrete it into the plasma in large amounts. Present data indicate that most mammals possess a single renin gene, however in most strains of mice there exists an additional gene, Ren-2, encoding a highly homologous but physically distinct enzyme renin-2. The two genes have different but often overlapping expression patterns, with both being expression at equal levels in the JG cells of the kidney (mRNA level). A major difference between the two enzyme is their capacity for N-linked glycosylation, renin-1d being glycosylated at one or more of its three potential glycosylation sites, whereas renin-2 is not glycosylated, lacking any N-linked glycosylation consensus sequences. To facilitate studies of the physiological significance of the two renin genes in mice, we have disrupted the Ren-1d gene by gene targeting, leaving renin-2 as the only functional renin isozyme capable of participating in the renin-angiotensin system. The targeting construct used to disrupt the Ren-1d gene was assembled using homology arms of 3.7 and 3.6kb generated by PCR. Ren-1d-/- animals are viable, display no gross, visible abnormalities and express Ren-2 as the only renin mRNA. The kidneys of all adult homozygous mutant animals display altered morphology of the macula densa and complete absence of JG cell granulation. Blood pressure homeostasis in these animals displays a sexual dimorphism, with female, but not male, Ren-1d-/- animals showing a reduced blood pressure. These results prove that renin-1d and renin-2 are not functionally equivalent enzymes, Ren-1d being required for normal macula densa cell morphology, granulation of JG cells and the maintenance of normal blood pressure in female Ren-1d-/- animals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.643194  DOI: Not available
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