RGD Reference Report - Unique quantitative trait loci in synergy permanently improve diastolic dysfunction. - Rat Genome Database

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Unique quantitative trait loci in synergy permanently improve diastolic dysfunction.

Authors: Chauvet, C  Crespo, K  Shi, Y  Gelinas, D  Duval, F  L'heureux, N  Nattel, S  Tardif, JC  Deng, AY 
Citation: Chauvet C, etal., Can J Cardiol. 2013 Oct;29(10):1302-9. doi: 10.1016/j.cjca.2013.03.012. Epub 2013 Jun 14.
RGD ID: 8657382
Pubmed: PMID:23773896   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cjca.2013.03.012   (Journal Full-text)

BACKGROUND: Diastolic dysfunction often precedes the onset of diastolic heart failure. We previously demonstrated that diastolic dysfunction and left ventricular hypertrophy (LVH) in Dahl salt-sensitive rats can be ameliorated by quantitative trait loci (QTLs). METHODS: We analyzed cardiac phenotypes of 2 "single" congenic strains, C10S.L33 and C10S.L28, by echocardiography, in which a specific Dahl salt-sensitive rat chromosome segment was replaced by its Lewis homologue. C10S.L33 improves diastolic function (DF) and LVH only in rats aged 10 weeks, not aged 15 weeks. C10S.L28 alleviated LVH, but not diastolic dysfunction. Thus, the QTLs captured by C10S.L33 and C10S.L28 are designated as DF/LVH C10QTL7 and LVH C10QTL4, respectively. We then combined multiple single strains to form 2 congenic combinations. One of the 2 congenic combinations included the chromosome segments covered by C10S.L33 and C10S.L28. RESULTS: Diastolic dysfunction was either completely or partially reversed by 15 weeks in the 2 congenic combinations. LVH was permanently improved from 10 to 15 weeks. CONCLUSIONS: Distinct QTLs exist that regulate diastolic function and/or LVH in the short term when acting alone, but durably when combined. The Ccl2 chemokine (C-C motif) ligand 1 (Ccl2) gene is the prime candidate for DF/LVH C10QTL7, owing to a nonconserved coding mutation. Schlafen genes are candidates for LVH C10QTL4. Since CCL2 and Schlafens are not known for influencing diastolic function and left ventricular mass, novel long-term strategies of prognosis, diagnosis, and therapy for diastolic heart failure and LVH appear from this work.

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Mammalian Phenotype
Objects referenced in this article
QTL Bp312 Blood pressure QTL 312 Rattus norvegicus
Strain SS.LEW-(D10Chm246-D10Chm257)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm214-D2Chm302)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm366-D2Rat52),LEW-(D18Rat61-D18Rat45),LEW-(D10Chm128-D10Chm121)/Ayd null Rattus norvegicus

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