Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage.
Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage.
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DOI：
10.1152/physiolgenomics.00103.2003
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发表时间：
2003-12
影响因子：
4.6
通讯作者：
A. Lionikas;A. Lionikas;D. Blizard;D. Vandenbergh;Marcus G. Glover;J. T. Stout;G. Vogler;G. Mcclearn;L. Larsson;Lars Larsson
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文献类型：
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作者：
A. Lionikas;A. Lionikas;D. Blizard;D. Vandenbergh;Marcus G. Glover;J. T. Stout;G. Vogler;G. Mcclearn;L. Larsson;Lars Larsson
该研究的目的是探索影响快肌和慢肌骨骼肌重量的遗传结构。 200 日龄 C57BL/6J (B6) 小鼠的慢肌、混合腓肠肌、快肌胫骨前肌 (TA) 和趾长伸肌 (EDL) 的重量比 DBA/2J (D2) 小鼠大 11-34% (P < 0.001)。男性肌肉比女性大 13-28%（P < 1 x 10(-5)，性别互动不会造成压力）。然而，肌肉重量的性别相关差异在 23 种衍生的 BXD 重组近交 (RI) 品系中存在显着差异（比目鱼肌性别相互作用的品系，P < 0.01；TA，P < 1 x 10(-4)；EDL，不显着；腓肠肌，P < 0.001）。在 B6 和 D2 小鼠 (B6D2F2) 和 BXD RI 的 F2 杂交中绘制了影响肌肉重量的数量性状基因座 (QTL)。在染色体 1（Chr 1）、2、3（女性特异性）、5（两条）、6、7、 B6D2F2 小鼠中为 8 和 9。 EDL 8 号染色体上的 QTL 和腓肠肌 3 号染色体上的雌性特异性 QTL 具有统计学显着性，但其余 QTL 处于统计学显着性提示水平。在 BXD RI 中鉴定出 Chr 1、2、4、5、7、8、14、17（两个）和 19 上的 10 个 QTL。 BXD RI 中的一半 QTL 具有多效性，并且处于提示性显着性水平（除了第 17 号腓肠肌的显着 QTL）。 B6D2F2 在 Chr 8 上指定的 EDL 权重 QTL 在 BXD RI 中得到了验证（P < 0.03）。 B6D2F2 和 BXD RI 之间 Chr 1 和 5 上 QTL 的支持区间重叠。 Chr 1 和 17 标记之间的上位相互作用影响 BXD RI 中腓肠肌的重量。然而，这种相互作用并未在 B6D2F2 群体中得到验证。我们的结果表明，B6 和 D2 分离群体中肌肉重量的差异是多基因系统的结果，每个因素对表型变异都有少量贡献，影响肌肉重量的遗传结构是肌肉特异性的，但不是肌肉类型特异性的，在某些情况下是性别特异性的。
The aim of the study was to explore the genetic architecture influencing weight of fast- and slow-twitch skeletal muscles. The weights of the slow-twitch soleus, the mixed gastrocnemius, the fast-twitch tibialis anterior (TA), and extensor digitorum longus (EDL) muscles were 11-34% greater (P < 0.001) in 200-day-old C57BL/6J (B6) than in DBA/2J (D2) mice. Male muscles were 13-28% larger than female (P < 1 x 10(-5), no strain by sex interaction). The sex-related difference in muscle weight, however, varied significantly among the 23 derivative BXD recombinant inbred (RI) strains (strain by sex interaction for soleus, P < 0.01; TA, P < 1 x 10(-4); EDL, not significant; and gastrocnemius, P < 0.001). Quantitative trait loci (QTL) affecting muscle weight were mapped in an F2 intercross of B6 and D2 mice (B6D2F2) and BXD RIs. A total of 10 autosomal, muscle-specific, but not muscle-type-specific, QTL, explaining a total of 5.4, 7.7, 22.9, and 8.6% of phenotypic variance for soleus, TA, EDL, and gastrocnemius muscles, respectively, were found across chromosomes 1 (Chr 1), 2, 3 (female-specific), 5 (two), 6, 7, 8, and 9 in B6D2F2 mice. The QTL on Chr 8 for EDL and the female-specific QTL on Chr 3 for gastrocnemius muscles were statistically significant, but the remaining QTL were at the suggestive level of statistical significance. Ten QTL on Chr 1, 2, 4, 5, 7, 8, 14, 17 (two), and 19 were identified in BXD RIs. Half of the QTL in BXD RIs had pleiotropic effects and were at the suggestive level of significance (except for the significant QTL for gastrocnemius muscle on Chr 17). The B6D2F2 nominated QTL on Chr 8 for EDL weight was validated in BXD RIs (P < 0.03). Support intervals for the QTL on Chr 1 and 5 overlapped between B6D2F2 and BXD RIs. An epistatic interaction between markers on Chr 1 and 17 affected gastrocnemius weight in BXD RIs. The interaction was not, however, validated in the B6D2F2 population. Our results indicate that the differences in muscle weight in the B6 and D2 segregating populations were the outcome of a polygenic system, with each factor contributing a small amount to the phenotypic variance and the genetic architecture affecting muscle weight was muscle specific, but not muscle-type specific, and in some instances sex specific.