Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00474003" target="_blank" >RIV/67985823:_____/17:00474003 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1242/dmm.026716" target="_blank" >http://dx.doi.org/10.1242/dmm.026716</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1242/dmm.026716" target="_blank" >10.1242/dmm.026716</a>

Result language

angličtina

Original language name

Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

Original language description

We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/GAP301%2F12%2F0696" target="_blank" >GAP301/12/0696: Transgenic rescue analysis of down-regulated genes involved in catecholamine biosynthesis in adrenal medulla of the spontaneously hypertensive rat</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Disease Models & Mechanisms

ISSN

1754-8403

e-ISSN

—

Volume of the periodical

10

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

297-306

UT code for WoS article

000395717100009

EID of the result in the Scopus database

2-s2.0-85018307139