Development of the National Institutes of Health Genetically Heterogeneous Rat Stock

Hansen, Carl T.; Spuhler, Karen

doi:10.1111/j.1530-0277.1984.tb05706.x

Cited by 265 publications

(199 citation statements)

References 7 publications

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“…The starting population was 23 female and 24 male genetically heterogeneous rats (N:NIH stock) obtained from a colony maintained at the National Institutes of Health (13). We requested that each rat in the founder population be of different parentage so that selection was not among brothers and sisters, which broadens the genetic variance (14).…”

Section: Methodsmentioning

confidence: 99%

“…All procedures were carried out with approval by our Institutional Animal Care and Use Committee and were conducted in accordance with the "Guiding Principles in the Care and Use of Animals" as approved by the American Physiological Society. The pretraining estimate of capacity for the founder rats was initiated after a 3-wk accommodation when the rats were [11][12][13][14][15][16][17][18][19] wk old. Rats were tested and trained between 4:00 PM and 8:00 PM, with the specific time of day for any rat randomized.…”

Section: Methodsmentioning

confidence: 99%

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Selected Contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats

Troxell

Britton

Koch

2003

Journal of Applied Physiology

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Troxell, Michael Lee, Steven Loyal Britton, and Lauren Gerard Koch. Selected Contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats. J Appl Physiol 94: 1674-1681, 2003. First published November 1, 2002 10.1152/japplphysiol.00851. 2002-Adaptational response to aerobic exercise was artificially selected for across one generation in a founder population of 20 female and 20 male genetically heterogeneous rats (N:NIH). Selection for low and high response was based on the change in treadmill running capacity, assessed by meters (m) run to exhaustion before and after 24 days of modest treadmill running. The training response of the founder population averaged ϩ222 m, with wide variation from a negative gain (Ϫ) of Ϫ110 m to a positive gain (ϩ) of ϩ430 m. Six pairs of the lowest (ϩ13 m) and highest (ϩ327 m) responders were mated. Mean response to training of the lowline (ϩ242 m) offspring did not differ from the founder. The high-selected line gained 383 m from training, ϩ161 m above the founder population. Narrow sense heritability estimated from regression of offspring on midparent values for response to training was 0.43 (P Ͻ 0.007). One generation of selection resulted in a 58% divide between the low and high lines. Selectively bred models of both intrinsic (untrained) and adaptation response can be useful in resolving the genetic basis of variation in aerobic capacity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Selected Contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats

Troxell

Britton

Koch

2003

Journal of Applied Physiology

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“…Briefly, artificial, two-way, selective breeding was used to create low and high strains for treadmill running capacity. The founder population was 80 male and 88 female genetically heterogeneous rats (N:NIH stock) obtained from a colony maintained at the National Institutes of Health (31). The protocol for estimation of endurance capacity required 2 wk and was started when the rats were 10 wk old (43).…”

Section: Experimental Subjectsmentioning

confidence: 99%

Reduced susceptibility to ventricular tachyarrhythmias in rats selectively bred for high aerobic capacity

Lujan

Britton²,

Koch

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Reduced susceptibility to ventricular tachyarrhythmias in rats selectively bred for high aerobic capacity. Am J Physiol Heart Circ Physiol 291: H2933-H2941, 2006. First published August 4, 2006 doi:10.1152/ajpheart.00514.2006.-Reperfusion after a brief period of cardiac ischemia can lead to potentially lethal arrhythmias. Human epidemiological studies and experimental work with animals indicate that regular physical activity is associated with reductions in cardiovascular disease (CVD) risk factors and sudden cardiac death. Similarly, artificial selection of rats for high aerobic treadmill-running capacity (high-capacity runners; HCR) has been shown to reduce CVD risk factors relative to rats selected as lowcapacity runners (LCR). Therefore, we tested the hypothesis that HCR, relative to LCR rats, would be less susceptible to ischemiareperfusion-mediated ventricular tachyarrhythmias. To test this hypothesis, we measured the susceptibility to ventricular tachyarrhythmias produced by 3 min of occlusion and reperfusion of the left main coronary artery in conscious LCR and HCR rats. Results document a significantly lower incidence of ventricular tachyarrhythmias in HCR (3 of 11, 27.3%) relative to LCR (6 of 7, 85.6%) rats. The decreased susceptibility to tachyarrhythmias in HCR rats was associated with a reduced cardiac metabolic demand during ischemia (lower rate-pressure product and ST segment elevation) as well as a wider range for the autonomic control of heart rate. The HCR and LCR represent a unique substrate for evaluation of the mechanisms underlying ischemia-mediated cardiac arrhythmogenesis. artificial selection; cardiovascular risks; arrhythmia; exercise TEMPORARY OCCLUSION of the coronary arteries can lead to potentially lethal arrhythmias (66,82). Coronary artery occlusion-induced arrhythmias are triggered by the ischemic insult directly or on relief of the ischemic insult during the reperfusion phase. The mechanisms underlying the ventricular arrhythmias during ischemia and reperfusion are related but distinct (5,56,75,82). Although ischemia is a more common trigger of sudden death than is reperfusion, life-threatening reperfusion arrhythmias are observed during relief of coronary spasm, during angioplasty or thrombolysis, and after cardiac surgery with ischemic arrest (24).

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“…We used an outbred population of rats descended from eight inbred progenitors (ACI/N, BN/SsN -a sub-strain of the reference strain BN, BUF/ N, F344/N, M520/N, MR/N, WKY/N and WN/N) through more than 60 generations of outbreeding 5,6 ( Figure 1). The Heterogeneous Stock (HS) was chosen for its potential for high-resolution mapping.…”

Section: Background and Summarymentioning

confidence: 99%

Erratum: Genomes and phenomes of a population of outbred rats and its progenitors

Baud¹,

Guryev²,

Hummel³

et al. 2014

Sci Data

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, The Rat Genome Sequencing and Mapping Consortium and Jonathan Flint 5Finding genetic variants that contribute to phenotypic variation is one of the main challenges of modern genetics. We used an outbred population of rats (Heterogeneous Stock, HS) in a combined sequence-based and genetic mapping analysis to identify sequence variants and genes contributing to complex traits of biomedical relevance. Here we describe the sequences of the eight inbred progenitors of the HS and the variants that segregate between them. We report the genotyping of 1,407 HS rats, and the collection from 2,006 rats of 195 phenotypic measures that are relevant to models of anxiety, type 2 diabetes, hypertension and osteoporosis. We make available haplotype dosages for the 1,407 genotyped rats, since genetic mapping in the HS is best carried out by reconstructing each HS chromosome as a mosaic of the progenitor genomes. Finally, we have deposited an R object that makes it easy to incorporate our sequence data into any genetic study of HS rats. Our genetic data are available for both Rnor3.4 and Rnor5.0 rat assemblies.

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Development of the National Institutes of Health Genetically Heterogeneous Rat Stock

Cited by 265 publications

References 7 publications

Selected Contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats

Selected Contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats

Reduced susceptibility to ventricular tachyarrhythmias in rats selectively bred for high aerobic capacity

Erratum: Genomes and phenomes of a population of outbred rats and its progenitors

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