Chromosomes 6 and 13 harbor genes that regulate pubertal timing in mouse chromosome substitution strains

Chromosomes 6 and 13 harbor genes that regulate pubertal timing in mouse chromosome substitution strains
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DOI:
10.1210/en.2004-0543
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发表时间:
2004-10-01
期刊:
影响因子:
4.8
通讯作者:
Palmert, MR
Palmert, MR
中科院分区:
医学2区
文献类型:
--
作者:
Krewson, TD;Supelak, PJ;Palmert, MR

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近交系小鼠青春期开始的变化表明,数量性状基因座(QTL)影响性成熟的神经和激素方面。采用一种新的方法来确定调节下丘脑-垂体-性腺(HPG)轴的因素,我们评估了两种近交系小鼠A/J和C57 BL/6 J(B6)以及A/J和B6小鼠产生的一组染色体置换株(CSS)的青春期时间[通过阴道开口(VO)评估]。在每个CSS中,来自A/J的单个染色体已经以纯合的方式取代了B6中的相应染色体,将A/J基因组划分为具有共同宿主(B6)背景的22个菌株。与B6小鼠相比,A/J小鼠的VO发生时间显著早于B6小鼠。虽然大多数评估的CSS具有与祖先B6品系相似的VO时间,但染色体6和13的CSS各自显示出比B6小鼠显著更早的VO时间。染色体6和13的F1(B6 x CSS)小鼠显示介于CSS和B6品系之间的表型,表明该性状以共显性方式遗传。这些结果表明,染色体6和13港QTL控制VO的时间。鉴定相关基因可能揭示调节HPG轴成熟和决定青春期时间的因素。
Variation in the onset of puberty among inbred strains of mice suggests that quantitative trait loci (QTLs) affect neurological and hormonal aspects of sexual maturation. Taking a novel approach toward identifying factors that regulate the hypothalamic-pituitary-gonadal (HPG) axis, we evaluated pubertal timing [ as assessed by vaginal opening (VO)] in two inbred strains of mice, A/J and C57BL/6J (B6), and in a panel of chromosome substitution strains (CSSs) generated from A/J and B6 mice. In each CSS, a single chromosome from A/J has been substituted in a homozygous fashion for the corresponding chromosome in B6, partitioning the A/J genome into 22 strains with a common host (B6) background. VO occurred significantly earlier in A/J compared with B6 mice. Although the majority of the CSSs assessed had a timing of VO that was similar to the progenitor B6 strain, CSSs for chromosomes 6 and 13 each displayed significantly earlier time of VO than B6 mice. F1 (B6 x CSS) mice for chromosomes 6 and 13 displayed phenotypes that were intermediate between the CSS and B6 strains, suggesting that the trait was inherited in a codominant manner. These findings demonstrate that chromosomes 6 and 13 harbor QTLs that control the timing of VO. Identification of the responsible genes may reveal factors that regulate the maturation of the HPG axis and determine the timing of puberty.