Abstract Selection experiments can elucidate the varying course of adaptive changes across generations. We examined the appendicular skeleton of house mice from four replicate High Runner (HR) lines bred for physical activity on wheels and four non‐selected Control (C) lines. HR mice reached apparent selection limits between generations 17 and 27, running ~3‐fold more than C. Studies at generations 11, 16, and 21 found that HR mice had evolved thicker hindlimb bones, heavier feet, and larger articular surface areas of the knee and hip joint. Based on biomechanical theory, any or all of these evolved differences may be beneficial for endurance running. Here, we studied mice from generation 68, plus a limited sample from generation 58, to test whether the skeleton continued to evolve after selection limits were reached. Contrary to our expectations, we found few differences between HR and C mice for these later generations, and some of the differences in bone dimensions identified in earlier generations were no longer statistically significant. We hypothesize that the loss of apparently coadapted lower‐level traits reflects (1) deterioration related to a gradual increase in inbreeding and/or (2) additional adaptive changes that replace the functional benefits of some skeletal changes. 
                        more » 
                        « less   
                    
                            
                            Evolution of hindlimb bone dimensions and muscle masses in house mice selectively bred for high voluntary wheel-running behavior
                        
                    
    
            We have used selective breeding with house mice to study coadaptation of morphology and physiology with the evolution of high daily levels of voluntary exercise. Here, we compared hindlimb bones and muscle masses from the 11th generation of four replicate High Runner (HR) lines of house mice bred for high levels of voluntary wheel running with four non‐selected control (C) lines. Mass, length, diameter, and depth of the femur, tibia‐fibula, and metatarsal bones, as well as masses of gastrocnemius and quadriceps muscles, were compared by analysis of covariance with body mass or body length as the covariate. Mice from HR lines had relatively wider distal femora and deeper proximal tibiae, suggesting larger knee surface areas, and larger femoral heads. Sex differences in bone dimensions were also evident, with males having thicker and shorter hindlimb bones when compared with females. Several interactions between sex, linetype, and/or body mass were observed, and analyses split by sex revealed several cases of sex‐specific responses to selection. A subset of the HR mice in two of the four HR lines expressed the mini‐muscle phenotype, characterized mainly by an ∼50% reduction in hindlimb muscle mass, caused by a Mendelian recessive mutation, and known to have been under positive selection in the HR lines. Mini‐muscle individuals had elongated distal elements, lighter and thinner hindlimb bones, altered 3rd trochanter muscle insertion positions, and thicker tibia‐fibula distal widths. Finally, several differences in levels of directional or fluctuating asymmetry in bone dimensions were observed between HR and C, mini‐ and normal‐muscled mice, and the sexes. This study demonstrates that skeletal dimensions and muscle masses can evolve rapidly in response to directional selection on locomotor behavior. 
        more » 
        « less   
        
    
                            - Award ID(s):
- 1655362
- PAR ID:
- 10055964
- Date Published:
- Journal Name:
- Journal of Morphology
- Volume:
- 0
- ISSN:
- 0362-2525
- Page Range / eLocation ID:
- xx-xx
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
- 
            
- 
            Abstract ObjectivesLittle is known about how ilium cortical bone responds to loading. Using a mouse model, this study presents data testing the hypothesis that iliac cross‐sectional properties are altered in response to increased activity. Materials and MethodsThe sample derives from lines of High Runner (HR) mice bred for increased wheel‐running activity. Four treatment groups of female mice were tested: non‐selected control lines housed without (N = 19) and with wheels (N = 20), and HR mice housed without (N = 17) and with wheels (N = 18) for 13 weeks beginning at weaning. Each pelvis was μCT‐scanned, cross‐sectional properties (cortical area—Ct.Ar, total area—Tt.Ar, polar moment of area, and polar section modulus) were determined from the ilium midshaft, and robusticity indices (ratio of the square root ofCt.ArorTt.Arto caudal ilium length) were calculated. Mixed models were implemented with linetype, wheel access, and presence of the mini‐muscle phenotype as fixed effects, replicate line nested within linetype as a random effect, and body mass as a covariate. ResultsResults demonstrate that the mouse ilium morphologically resembles a long bone in cross section. Body mass and the mini‐muscle phenotype were significant predictors of iliac cross‐sectional properties. Wheel access only had a statistically significant effect onCt.Arand its robusticity index, with greater values in mice with wheel access. DiscussionThese results suggest that voluntary exercise increases cortical area, but does not otherwise strengthen the ilium in these mice, corroborating previous studies on the effect of increased wheel‐running activity on femoral and humeral cross‐sectional properties in these mice.more » « less
- 
            Abstract Bone modeling and remodeling are aerobic processes that entail relatively high oxygen demands. Long bones receive oxygenated blood from nutrient arteries, epiphyseal‐metaphyseal arteries, and periosteal arteries, with the nutrient artery supplying the bulk of total blood volume in mammals (~ 50–70%). Estimates of blood flow into these bones can be made from the dimensions of the nutrient canal, through which nutrient arteries pass. Unfortunately, measuring these canal dimensions non‐invasively (i.e. without physical sectioning) is difficult, and thus researchers have relied on more readily visible skeletal proxies. Specifically, the size of the nutrient artery has been estimated from dimensions (e.g. minimum diameters) of the periosteal (external) opening of the nutrient canal. This approach has also been utilized by some comparative morphologists and paleontologists, as the opening of a nutrient canal is present long after the vascular soft tissue has degenerated. The literature on nutrient arteries and canals is sparse, with most studies consisting of anatomical descriptions from surgical proceedings, and only a few investigating the links between nutrient canal morphology and physiology or behavior. The primary objective of this study was to evaluate femur nutrient canal morphology in mice with known physiological and behavioral differences; specifically, mice from an artificial selection experiment for high voluntary wheel‐running behavior. Mice from four replicate high runner (HR) lines are known to differ from four non‐selected control (C) lines in both locomotor and metabolic activity, withHRmice having increased voluntary wheel‐running behavior and maximal aerobic capacity (VO2max) during forced treadmill exercise. Femora from adult mice (average age 7.5 months) of the 11th generation of this selection experiment were μCT‐scanned and three‐dimensional virtual reconstructions of nutrient canals were measured for minimum cross‐sectional area as a skeletal proxy of blood flow. Gross observations revealed that nutrient canals varied far more in number and shape than prior descriptions would indicate, regardless of sex or genetic background (i.e.HRvs. C lines). Canals adopted non‐linear shapes and paths as they traversed from the periosteal to endosteal borders through the cortex, occasionally even branching within the cortical bone. Additionally, mice from bothHRand C lines averaged more than four nutrient canals per femur, in contrast to the one to two nutrient canals described for femora from rats, pigs, and humans in prior literature. Mice fromHRlines had significantly larger total nutrient canal area than C lines, which was the result not of an increase in the number of nutrient canals, but rather an increase in their average cross‐section size. This study demonstrates that mice with an evolutionary history of increased locomotor activity and maximal aerobic metabolic rate have a concomitant increase in the size of their femoral nutrient canals. Although the primary determinant of nutrient canal size is currently not well understood, the present results bolster use of nutrient canal size as a skeletal indicator of aerobically supported levels of physical activity in comparative studies.more » « less
- 
            ABSTRACT In general, sustained high rates of physical activity require a high maximal aerobic capacity (V̇O2,max), which may also necessitate a high basal aerobic metabolism (BMR), given that the two metabolic states are linked via shared organ systems, cellular properties and metabolic pathways. We tested the hypotheses that (a) selective breeding for high voluntary exercise in mice would elevate both V̇O2,max and BMR, and (b) these increases are accompanied by increases in the size of some internal organs (ventricle, triceps surae muscle, liver, kidney, spleen, lung, brain). We measured 72 females from generations 88 and 96 of an ongoing artificial selection experiment comprising four replicate High Runner (HR) lines bred for voluntary daily wheel-running distance and four non-selected control lines. With body mass as a covariate, HR lines as a group had significantly higher V̇O2,max (+13.6%, P<0.0001), consistent with previous studies, but BMR did not significantly differ between HR and control lines (+6.5%, P=0.181). Additionally, HR mice did not statistically differ from control mice for whole-body lean or fat mass, or for the mass of any organ collected (with body mass as a covariate). Finally, mass-independent V̇O2,max and BMR were uncorrelated (r=0.073, P=0.552) and the only statistically significant correlation with an organ mass was for V̇O2,max and ventricle mass (r=0.285, P=0.015). Overall, our results indicate that selection for a behavioral trait can yield large changes in behavior without proportional modifications to underlying morphological or physiological traits.more » « less
- 
            Abstract The nutrient artery provides ~50%–70% of the total blood volume to long bones in mammals. Studying the functional characteristics of this artery in vivo can be difficult and expensive, so most researchers have measured the nutrient foramen, an opening on the outer surface of the bone that served as the entry point for the nutrient artery during development and bone ossification. Others have measured the nutrient canal (i.e., the passage which the nutrient artery once occupied), given that the external dimensions of the foramen do not necessarily remain uniform from the periosteal surface to the medullary cavity. The nutrient canal, as an indicator of blood flow to long bones, has been proposed to provide a link to studying organismal activity (e.g., locomotor behavior) from skeletal morphology. However, although external loading from movement and activity causes skeletal remodeling, it is unclear whether it affects the size or configuration of nutrient canals. To investigate whether nutrient canals can exhibit phenotypic plasticity in response to physical activity, we studied a mouse model in which four replicate high runner (HR) lines have been selectively bred for high voluntary wheel‐running behavior. The selection criterion is the average number of wheel revolutions on days 5 and 6 of a 6‐day period of wheel access as young adults (~6–8 weeks old). An additional four lines are bred without selection to serve as controls (C). For this study, 100 female mice (half HR, half C) from generation 57 were split into an active group housed with wheels and a sedentary group housed without wheels for 12 weeks starting at ~24 days of age. Femurs were collected, soft tissues were removed, and femora were micro‐computed tomography scanned at a resolution of 12 μm. We then imported these scans into AMIRA and created 3D models of femoral nutrient canals. We tested for evolved differences in various nutrient canal traits between HR and C mice, plastic changes resulting from chronic exercise, and the selection history‐by‐exercise interaction. We found few differences between the nutrient canals of HR versus C mice, or between the active and sedentary groups. We did find an interaction between selection history and voluntary exercise for the total number of nutrient canals per femur, in which wheel access increased the number of canals in C mice but decreased it in HR mice. Our results do not match those from an earlier study, conducted at generation 11, which was prior to the HR lines reaching selection limits for wheel running. The previous study found that mice from the HR lines had significantly larger total canal cross‐sectional areas compared to those from C lines. However, this discrepancy is consistent with studies of other skeletal traits, which have found differences between HR and C mice to be somewhat inconsistent across generations, including the loss of some apparent adaptations with continued selective breeding after reaching a selection limit for wheel‐running behavior.more » « less
 An official website of the United States government
An official website of the United States government 
				
			 
					 
					
 
                                    