Journal article
A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical Hindlimb ischemia
Circulation (New York, N.Y.), Vol.117(9), pp.1207-1215
03/04/2008
DOI: 10.1161/CIRCULATIONAHA.107.736447
PMCID: PMC2881228
PMID: 18285563
Abstract
Background-Peripheral arterial disease ( PAD) caused by occlusive atherosclerosis of the lower extremity has 2 major clinical manifestations. Critical limb ischemia is characterized by rest pain and/or tissue loss and has a >= 40% risk of death and major amputation. Intermittent claudication causes pain on walking, has no tissue loss, and has amputation plus mortality rates of 2% to 4% per year. Progression from claudication to limb ischemia is infrequent. Risk factors in most PAD patients overlap. Thus, we hypothesized that genetic variations may be linked to presence or absence of tissue loss in PAD.
Methods and Results-Hindlimb ischemia (murine model of PAD) was induced in C57BL/6, BALB/c, C57BL/6 x BALB/c (F1), F1 x BALB/c (N2), A/J, and C57BL/6J- Chr7(A/J)/NaJ chromosome substitution strains. Mice were monitored for perfusion recovery and tissue necrosis. Genome-wide scanning with polymorphic markers across the 19 murine autosomes was performed on the N2 mice. Greater tissue loss and poorer perfusion recovery occurred in BALB/c than in the C57BL/6 strain. Analysis of 105 N2 progeny identified a single quantitative trait locus on chromosome 7 that exhibited significant linkage to both tissue necrosis and extent of perfusion recovery. Using the appropriate chromosome substitution strain, we demonstrate that C57BL/6-derived chromosome 7 is required for tissue preservation.
Conclusions-We have identified a quantitative trait locus on murine chromosome 7 (LSq-1) that is associated with the absence of tissue loss in a preclinical model of PAD and may be useful in identifying gene(s) that influence PAD in humans.
Details
- Title: Subtitle
- A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical Hindlimb ischemia
- Creators
- Ayotunde O Dokun - Duke Univ, Div Endocrinol, Durham, NC 27710 USASehoon Keum - Duke University Medical CenterSurovi Hazarika - Duke University Medical CenterYongjun Li - Duke University Medical CenterGregory M. Lamonte - Duke University Medical CenterFerrin Wheeler - Duke University Medical CenterDouglas A. Marchuk - Duke University Medical CenterBrian H. Annex - Duke Medical Center
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.117(9), pp.1207-1215
- DOI
- 10.1161/CIRCULATIONAHA.107.736447
- PMID
- 18285563
- PMCID
- PMC2881228
- NLM abbreviation
- Circulation
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 9
- Grant note
- T32HL007101 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 HL755752; T32 HL007101; R01 HL097281-02; R01 HL097281; R01 HL097281-01 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 03/04/2008
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984297595302771
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