Contractile abilities of normal and “mini” triceps surae muscles from mice (Mus domesticus) selectively bred for high voluntary wheel running

Abstract

Contractile abilities of normal and "mini" triceps surae muscles from mice (Mus domesticus) selectively bred for high voluntary wheel running. J Appl Physiol 99: 1308 -1316, 2005. First published June 9, 2005; doi:10.1152/japplphysiol.00369.2005.-As reported previously, artificial selection of house mice caused a 2.7-fold increase in voluntary wheel running of four replicate selected lines compared with four random-bred control lines. Two of the selected lines developed a high incidence of a small-muscle phenotype ("mini muscles") in the plantar flexor group of the hindlimb, which apparently results from a simple Mendelian recessive allele. At generations 36 -38, we measured wheel running and key contractile characteristics of soleus and medial gastrocnemius muscles from normal and mini muscles in mice from these selected lines. Mice with mini muscles ran faster and a greater distance per day than normal individuals but not longer. As expected, in minimuscle mice the medial and lateral gastrocnemius muscles were ϳ54 and 45% the mass of normal muscles, respectively, but the plantaris muscles were not different in mass and soleus muscles were actually 30% larger. In spite of the increased mass, contractile characteristics of the soleus were unchanged in any notable way between mini and normal mice. However, medial gastrocnemius muscles in mini mice were changed markedly toward a slower phenotype, having slower twitches; demonstrated a more curved force-velocity relationship; produced about half the massspecific isotonic power, 20 -50% of the mass-specific cyclic work and power (only 10 -25% the absolute power if the loss in mass is considered); and fatigued at about half the rate of normal muscles. These changes would promote increased, aerobically supported running activity but may compromise activities that require high power, such as sprinting. experimental evolution; fatigue; muscle mechanics; power; selective breeding; work SWALLOW ET AL. (34) describe an artificial selection experiment using a base population of outbred, Hsd:ICR house mice (Mus domesticus) in which four replicate lines were subject to selective breeding for high levels of voluntary wheel running whereas another four lines were random bred as controls. Compared with mice from the control lines, mice from the selected lines ran ϳ70% more revolutions/day after 10 generations of selection (34), 100% more after 14 generations (17), and 170% more revolutions and about double the average running speed after 23 generations (5, 11, 13). These mice have been the focus of anatomical, behavioral, physiological, and psychological investigations on the correlated effects of such selection (e.g., Refs. 7,11,[23][24][25]28,29,[35][36][37].More recently it has been noted that some individuals in both the selected and control lines express a small-muscle phenotype in which the plantar flexor muscle group (soleus, gastrocnemius, and plantaris) is 44 -50% lighter than normal for the body mass (5, 12, 17). Evidence suggests that this smallmuscle phenotype, coine...

A Novel Intronic Single Nucleotide Polymorphism in the Myosin heavy polypeptide 4 Gene Is Responsible for the Mini-Muscle Phenotype Characterized by Major Reduction in Hind-Limb Muscle Mass in Mice

“…In general, this includes changes in muscle mass, reduced body mass, larger hearts, no overt differences in locomotor behavior, reduced grip strength (K. M. Middleton, R. M. Hannon, and T. Garland Jr., unpublished results), reduced muscle force (Syme et al 2005;McGillivray et al 2009), and ultrastructural and histological differences (Guderley et al 2006(Guderley et al , 2008. In contrast, several findings in the Myh4 knockout strain do not closely match data from mini-muscle mice.…”

“…Initially, the phenotype remained at low frequency in the C line and eventually disappeared, but increased dramatically in frequency in both HR lines, eventually going to fixation in one of the two HR lines by approximately generation 36 (Syme et al 2005). Evidence for the adaptive significance of the allele was obtained by fitting multiple-generation data to hierarchical models that included effects of selection and/ or random genetic drift (Garland et al 2002).…”

“…The minimuscle allele was estimated to have been present at a frequency of 7% in the base population, and analyses indicated that strong selection favored the allele in the HR but not in the C lines. It was hypothesized that the mini-muscle phenotype has functional characteristics that facilitate high levels of wheel running (Garland et al 2002), such as a doubled mass-specific aerobic capacity (Houle-Leroy et al 2003) and increased fatigue resistance in at least some hind-limb muscles (Syme et al 2005). Alternatively, the underlying allele might have pleiotropic effects that act on nonmuscle tissues and organs but still facilitate endurance running (e.g., reduced total body mass and fat mass; increased relative heart, liver, and kidney mass; longer hind-limb bones) (Garland et al 2002;Kelly et al 2006;Hannon et al 2008;Kolb et al 2010).…”

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

“…Pleiotropic effects of this Mendelian recessive allele are many and varied, and include alterations in muscle fiber-type composition (fewer type IIb fibers), 26 contractile properties, 27 a doubling of mass-specific aerobic capacity and hexokinase activity, 14,24 increased glycogen concentration in gastrocnemius, 9 increased myoglobin concentration in medial gastrocnemius, 14 and increased heart ventricle mass. 13 Mini-muscle individuals run faster on wheels, and run more total revolutions per day under some conditions.…”

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

“…Degrees of freedom for testing the effects of line type, sex and the line type × sex interaction were always 1 and 6. Body mass was used as a covariate in these analyses, but age was not because retired male breeders were sampled earlier than female breeders, thus confounding age and sex.An unexpected finding of the selection experiment has been the discovery and increase in frequency, within two of the four HR lines, of individuals bearing the so-called mini-muscle phenotype (the result of a Mendelian recessive allele), recognized primarily by a reduction of ~50% in hindlimb muscle mass (Garland et al, 2002;Houle-Leroy et al, 2003;Syme et al, 2005;Wong et al, 2009). Mini-muscle individuals also differ from wild-type individuals in the size of some internal organs, including the heart, liver, spleen, lungs and kidneys [adjusting for variation in body size (e.g.…”