Quantitative Trait Loci Determining Weight Reduction of Testes and Pituitary by Diethylstilbesterol in LEXF and FXLE Recombinant Inbred Strain Rats

Tachibana, Masayoshi; Лу, Л.; Hayashi, Hiroshi; Tamura, Atsushi; Matsushima, Yoshibumi; Shisa, Hayase

doi:10.1538/expanim.55.91

Cited by 15 publications

(13 citation statements)

References 13 publications

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“…2, which reflects their historical breeding processes and substrains as previously described (20,23).…”

Section: Genetic Featuresmentioning

confidence: 79%

“…Even though the majority of the listed QTLs were obtained from F2 or backcross studies, one could be misled to underestimate the role of recombinant inbred (RI) lines since they have been utilized in rodents for more than 40 years (3,4,7,15,25). However, the majority of the RI lines originated from mouse strains, and only a few rat-derived RI lines are or were available (1,8,18,20,23).Successful QTL mapping always depends on diverse phenotypes and genotypes and a statistical method for determining the odds between phenotype and genotype patterns. This diversification of phenotypes combined with numerous recombination events across the rat genome are given requirements for the largest RI rat strain set available, the LEXF/FXLE strains, which were historically generated to study genes involved in tumor genesis.…”

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confidence: 99%

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confidence: 99%

“…These sublines are indicated by the letters B-D following the strain number, e.g., LEXF8D. Further details on the history of these RI strains are described elsewhere (20,23). The following strains were used for this study, with the inbred generations indicated in parentheses:…”

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confidence: 99%

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Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of complex traits

Voigt

Kuramoto

Mashimo

et al. 2008

Physiological Genomics

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Recombinant inbred (RI) strains are formed from an outcross between two well-characterized inbred stains followed by at least 20 generations of inbreeding. RI strains can be utilized for the analysis of many complex phenotypic traits. The LEXF/FXLE RI strain set consists of 34 RI strains derived by reciprocal crossing of LE/Stm and F344/Stm. Here we report on genetic dissections of complex traits using this RI set and their parental strains. We have developed strain distribution patterns for 232 informative simple sequence length polymorphism markers. The framework map covers the rat genome except for chromosome Y. Seventy-six phenotype parameters, which included physiological and behavioral traits, were examined for these RI lines. Quantitative trait locus (QTL) analysis of these parameters revealed 27 significant and 91 suggestive QTLs, illustrating the potential of this RI resource for the detection of underlying gene functions for various phenotypes. Although this RI set was originally developed to study susceptibility to chemical-induced tumors, it has been shown to be equally powerful for a wide spectrum of traits. The LEXF/FXLE RI strains have been deposited at the National Bio Resource Project for the Rat in Japan and are maintained under specific pathogen-free conditions. They are available at http://www.anim.med.kyoto-u.ac.jp/nbr.

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“…2, which reflects their historical breeding processes and substrains as previously described (20,23).…”

Section: Genetic Featuresmentioning

confidence: 79%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of complex traits

Voigt

Kuramoto

Mashimo

et al. 2008

Physiological Genomics

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“…Treatment with DES identified QTL influencing repression on chromosome 10 ( Esta1 ) and chromosome 2 ( Esta2 and Esta3 ) in a study using male F2 progeny from a BN x ACI intercross (Gould et al 2006). QTL associated with regression of testes induced by DES were identified on chromosomes 1 and 7 (Figure 1) in recombinant inbred male rats (Tachibana et al 2006). Although no linkage was detected for pituitary adenoma development in male rats in the recombinant inbred strains, the markers associated with regression of testes ( D1Wox25, D7Mit4 ) are in close proximity to a locus affecting pituitary adenomas on chromosome 1 ( Ept10 ) and the locus involved in mammary tumors and pituitary adenomas ( Emca4, Ept7 ) on chromosome 7 (Figure 1).…”

Section: Genetic Variants Determining Responses To Estrogenmentioning

confidence: 99%

Genetic variation in sensitivity to estrogens and breast cancer risk

et al. 2018

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Breast cancer risk is intimately intertwined with exposure to estrogens. While more than 160 breast cancer risk loci have been identified in humans, genetic interactions with estrogen exposure remain to be established. Strains of rodents exhibit striking differences in their responses to endogenous ovarian estrogens (primarily 17β-estradiol). Similar genetic variation has been observed for synthetic estrogen agonists (ethinyl estradiol) and environmental chemicals that mimic the actions of estrogens (xenoestrogens). This review of literature highlights the extent of variation in responses to estrogens among strains of rodents and compiles the genetic loci underlying pathogenic effects of excessive estrogen signaling. Genetic linkage studies have identified a total of the 35 quantitative trait loci (QTL) affecting responses to 17β-estradiol or diethylstilbestrol in 5 different tissues. However, the QTL appear to act in a tissue-specific manner with 9 QTL affecting the incidence or latency of mammary tumors induced by 17β-estradiol or diethylstilbestrol. Mammary gland development during puberty is also exquisitely sensitive to the actions of endogenous estrogens. Analysis of mammary ductal growth and branching in 43 strains of inbred mice identified 20 QTL. Regions in the human genome orthologous to the mammary development QTL harbor loci associated with breast cancer risk or mammographic density. The data demonstrate extensive genetic variation in regulation of estrogen signaling in rodent mammary tissues that alters susceptibility to tumors. Genetic variants in these pathways may identify a subset of women who are especially sensitive to either endogenous estrogens or environmental xenoestrogens and render them at increased risk of breast cancer.

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Rat Genome Mapping and Genomics

Szpirer

Levan²

2012

Genome Mapping and Genomics in Laboratory Animals

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Quantitative Trait Loci Determining Weight Reduction of Testes and Pituitary by Diethylstilbesterol in LEXF and FXLE Recombinant Inbred Strain Rats

Cited by 15 publications

References 13 publications

Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of complex traits

Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of complex traits

Genetic variation in sensitivity to estrogens and breast cancer risk

Rat Genome Mapping and Genomics

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