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Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse model

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Abstract

The FGS/Kist strain of mice, a new animal model for focal glomerulosclerosis (FGS) in humans, was previously established by recurrent selection for high proteinuria, which is a principal marker of FGS, from descendants of CBA/Nga and RFM/Nga strains. We performed a genome-wide scan for quantitative trait loci (QTLs) affecting proteinuria in a population of 356 backcross progeny derived from a cross between FGS/Kist and the standard normal strain, C57BL/6J. Five proteinuria QTLs (Ptnu1–5) were detected at the genome-wide 5% or less level. Ptnu1 and Ptnu2, located on Chromosomes (Chrs) 8 and 17, respectively, had main effects on proteinuria and also interacted epistatically with each other. However, Ptnu3 on Chr 9 and Ptnu4 and Ptnu5 both on Chr 15 had epistatic interaction effects only. Except for the epistatic interaction effect of Ptnu4 and Ptnu5, all alleles derived from FGS/Kist were responsible for the high proteinuria. These results indicated that the genetic control of proteinuria is complex and the identified QTLs may provide new insights into the pathogenesis of FGS in mice as well as in humans.

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Acknowledgments

This work was supported by two research grants from the Korea–Japan Basic Scientific Promotion Program of Korea Science and Engineering Foundation (20006-209-01-2) to J.G. Suh, and the Japan–Korea Joint Research Project, JSPS (00-3-90) to T. Namikawa and A. Ishikawa. We acknowledge Samuel Adjei for polishing the English.

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Authors and Affiliations

  1. Laboratory of Animal Genetics, Division of Applied Genetics and Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan

    Eun-Hee Kim, Takao Namikawa & Akira Ishikawa

  2. Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Taejon, 305-333, Korea

    Chul-Ho Lee & Byung-Hwa Hyun

  3. Department of Medical Genetics/Experimental Animal Center, College of Medicine, Hallym University, Chunchon, 200-702, Korea

    Jun-Gyo Suh & Yang-Seok Oh

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  1. Eun-Hee Kim
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  2. Chul-Ho Lee
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  4. Jun-Gyo Suh
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  6. Takao Namikawa
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  7. Akira Ishikawa
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Correspondence to Akira Ishikawa.

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Kim, EH., Lee, CH., Hyun, BH. et al. Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse model. Mamm Genome 16, 242–250 (2005). https://doi.org/10.1007/s00335-004-3023-7

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  • DOI: https://doi.org/10.1007/s00335-004-3023-7

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