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Asian-Australas J Anim Sci > Accepted Articles
DOI: https://doi.org/10.5713/ajas.18.0783    [Accepted] Published online March 7, 2019.
Effects of quantitative trait loci determining testicular weight in DDD/Sgn inbred mice are strongly influenced by circulating testosterone levels
Jun-ichi Suto1,*  , Misaki Kojima2
1Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki 305-8634, Japan
2Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki 305-0901, Japan
Correspondence:  Jun-ichi Suto, Tel: +81-29-838-6052, Fax: +81-29-838-6028, Email: jsuto@affrc.go.jp
Received: 17 October 2018   • Revised: 18 February 2019   • Accepted: 6 March 2019
Abstract
Objective: Testicular growth and development are strongly influenced by androgen. Although both testis weight and plasma testosterone level are inherited traits, the interrelationship between them is not fully established. Males of DDD/Sgn (DDD) mice are known to have extremely heavy testes and very high plasma testosterone level among inbred mouse strains. We dissected the genetic basis of testis weight and analyzed the potential influence of plasma testosterone level in DDD mice.

Methods

Quantitative trait loci (QTL) mapping of testis weight was performed with or without considering the influence of plasma testosterone level in reciprocal F2 intercross populations between DDD and C57BL/6J (B6) mice, thereby assessing the influence of testosterone on the effect of testis weight QTL. Candidate genes for testis weight QTL were investigated by next-generation sequencing analysis.

Results

Four significant QTL were identified on chromosomes 1, 8, 14, and 17. The DDD-derived allele was associated with increased testis weight. The F2 mice were then divided into two groups according to the plasma testosterone level (F2 mice with relatively “low” and “high” testosterone level), and QTL scans were again performed. Although QTL on chromosomes 1 was shared in both F2 mice, QTL on chromosomes 8 and 17 were identified specifically in F2 mice with relatively high testosterone levels. By whole-exome sequencing analysis, we identified one DDD-specific missense mutation Pro29Ser in Atat1.
Conclusion
Most of the testis weight QTL expressed stronger phenotypic effect when they were placed on circumstance with high testosterone level. High testosterone influenced the QTL by enhancing the effect of DDD-derived allele and diminishing the effects of B6-derived allele. Since Pro29Ser was not identified in other inbred mouse strains, and since Pro29 in Atat1 has been strongly conserved among mammalian species, Atat1 is a plausible candidate for testis weight QTL on chromosome 17.
Keywords: DDD/Sgn Mice; Quantitative Trait Loci (QTL) Mapping; Testis Weight; Testosterone Level; Whole-Exome Sequence Analysis
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