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Quantitative trait ...
Quantitative trait loci associated with angiotensin II and high-salt diet induced acute decompensated heart failure in Balb/CJ mice
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- Becirovic Agic, Mediha (author)
- Uppsala universitet,Integrativ Fysiologi
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- Jönsson, Sofia (author)
- Uppsala universitet,Integrativ Fysiologi
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- Hultström, Michael, 1978- (author)
- Uppsala universitet,Integrativ Fysiologi,Anestesiologi och intensivvård
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(creator_code:org_t)
- AMER PHYSIOLOGICAL SOC, 2019
- 2019
- English.
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In: Physiological Genomics. - : AMER PHYSIOLOGICAL SOC. - 1094-8341 .- 1531-2267. ; 51:7, s. 279-289
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Abstract
Subject headings
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- Genetic background of different mouse strains determines their susceptibility to disease. We have previously shown that Balb/CJ and C57BL/6J mice develop cardiac hypertrophy to the same degree when treated with a combination of angiotensin II and high-salt diet (ANG II+ Salt). but only Balb/CJ show impaired cardiac function associated with edema development and substantial mortality. We hypothesized that the different response to ANG II +Salt is due to the different genetic backgrounds of Balb/CJ and C57BL/6J. To address this we performed quantitative trait locus (QTL) mapping of second filial generation (F2) of mice derived from a backcross between Balb/CJ and first filial generation (Fl) of mice. Cardiac function was measured with echocardiography, glomerular filtration rate using FITC-inulin clearance, fluid and electrolyte balance in metabolic cages, and blood pressure with tail-cuff at baseline and on the fourth day of treatment with ANG II+Salt. A total of nine QTLs were found to be linked to different phenotypes in ANG II + Salt-treated F2 mice. A QTL on chromosome 3 was linked to cardiac output. and a QTL on chromosome 12 was linked to isovolumic relaxation time. QTLs on chromosome 2 and 3 were linked to urine excretion and sodium excretion. Eight genes located at the different QTLs contained coding nonsynonymous SNPs published in the mouse genome database that differ between Balb/CJ and C57BL/6J. In conclusion. ANG II+Salt-induced acute decompensation in Balb/CJ is genetically linked to several QTLs, indicating a multifaceted phenotype. The present study identified potential candidate genes that may represent important pathways in acute decompensated heart failure.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- acute decompensated heart failure
- angiotensin II
- genetic susceptibility
- high-salt diet
- QTL
Publication and Content Type
- ref (subject category)
- art (subject category)
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