Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.660166
Title: Characterisation of rat lines transgenic for the mouse Ren-2d cDNA
Author: Ogg, Donald
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Abstract:
The rat strain TGR (mRen-2)27 expresses the mouse genomic Ren-2d transgene in a tissue specific manner. The expression of this transgene results in elevated levels of prorenin in the plasma and adrenal gland, leading to fulminant hypertension by 12 weeks of age. The transgene expression pattern in the TGR(mRen-2)27 is not restricted to the adrenal gland but is present in the kidneys, testes, coagulating gland and other tissues. This makes establishing the exact role prorenin plays in the phenotype more complicated and to circumvent this we designed a transgene which expresses mouse Ren-2 prorenin from a site distant to the kidney juxtaglomerular cells. In the rat, only the juxtaglomerular cells are known to activate prorenin to renin. The effect of overexpressing prorenin, from a non-renal source, was investigated by directing expression of the mouse renin cDNA, Ren-2d, to the liver of transgenic rats. The transgene consisted of the promoter elements of the human a1 anti-trypsin gene fused to the mouse Ren-2 cDNA and was introduced into the rat genome by microinjection. Lines were established, from founder animals carrying the transgene, in both Sprague-Dawley and Fischer rat strains, and those which demonstrated the highest blood pressures were examined in detail. Expression analysis of the transgene in these lines showed detectable expression only in the liver, and an elevation of plasma prorenin with no increase in plasma active renin. All lines studied showed a pronounced cardiac hypertrophy at an early age, which in the case of the Fischer lines TGR(ProRen-2)7403 and TGR(ProRen-2)7651, was quantified by echocardiography. At six weeks of age lines TGR(ProRen-2) and TGR(ProRen-2)7651 showed left ventricular mass indices (LVMI) of 3.5 as opposed to controls showing LVMI of 1.6 at the same age. The percentage of plasma active renin that was transgene derived was greater than 80%, in all lines studied despite plasma active renin levels being normal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.660166  DOI: Not available
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