Published in
Lippincott, Williams & Wilkins, Journal of Hypertension, 5(34), p. 950-958, 2016
DOI: 10.1097/hjh.0000000000000875
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Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22
,
Francine Z. Marques,
Guillermo Lopez-Campos,
Scott A. Booth,
Maree McGlynn,
Paul Lewandowski,
Lea M. D. Delbridge,
Stephen B. Harrap,
Fadi J. Charchar
Full text: Unavailable
Abstract
BACKGROUND: Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR). METHODS AND RESULTS: To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHR × NHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P