Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage

Arimantas Lionikas, D A Blizard, D J Vandenbergh, M G Glover, J T Stout, G P Vogler, G E McClearn, L Larsson

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)141-152
Number of pages12
JournalPhysiological Genomics
Volume16
Issue number1
DOIs
Publication statusPublished - 2003

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Inbred DBA Mouse
Quantitative Trait Loci
Inbred C57BL Mouse
Skeletal Muscle
Weights and Measures
Muscles
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 17
Sex Characteristics
Population

Keywords

  • Aging
  • Animals
  • Body Weight
  • Epistasis, Genetic
  • Female
  • Lod Score
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Muscle Fibers, Fast-Twitch
  • Muscle Fibers, Slow-Twitch
  • Muscle, Skeletal
  • Organ Size
  • Phenotype
  • Quantitative Trait Loci
  • Sex Characteristics

Cite this

Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage. / Lionikas, Arimantas; Blizard, D A; Vandenbergh, D J; Glover, M G; Stout, J T; Vogler, G P; McClearn, G E; Larsson, L.

In: Physiological Genomics, Vol. 16, No. 1, 2003, p. 141-152.

Research output: Contribution to journalArticle

Lionikas, Arimantas ; Blizard, D A ; Vandenbergh, D J ; Glover, M G ; Stout, J T ; Vogler, G P ; McClearn, G E ; Larsson, L. / Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage. In: Physiological Genomics. 2003 ; Vol. 16, No. 1. pp. 141-152.
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abstract = "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.",
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TY - JOUR

T1 - Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage

AU - Lionikas, Arimantas

AU - Blizard, D A

AU - Vandenbergh, D J

AU - Glover, M G

AU - Stout, J T

AU - Vogler, G P

AU - McClearn, G E

AU - Larsson, L

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - Aging

KW - Animals

KW - Body Weight

KW - Epistasis, Genetic

KW - Female

KW - Lod Score

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Inbred DBA

KW - Muscle Fibers, Fast-Twitch

KW - Muscle Fibers, Slow-Twitch

KW - Muscle, Skeletal

KW - Organ Size

KW - Phenotype

KW - Quantitative Trait Loci

KW - Sex Characteristics

U2 - 10.1152/physiolgenomics.00103.2003

DO - 10.1152/physiolgenomics.00103.2003

M3 - Article

C2 - 14679300

VL - 16

SP - 141

EP - 152

JO - Physiological Genomics

JF - Physiological Genomics

SN - 1094-8341

IS - 1

ER -