Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (Po, Po/mg and Po/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased Po and an inability to sustain Po for the 300 ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology.

Brown M, Booth FW. Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances. Am J Physiol Regul Integr Comp Physiol 304: R1024-R1035, 2013. First published April 3, 2013 doi:10.1152/ajpregu.00581.2012.-The purpose of the present study was to partially phenotype male and female rats from generations 8 -10 (G8 -G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P Ͻ 0.001), spent less time running (P Ͻ 0.001), and ran slower (P Ͻ 0.001) than their G8 male and female HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1␣ mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9 -G10 LVR nonrunners vs. G9 -G10 HVR nonrunners (P ϭ 0.06), body fat percentage was similar between lines. G9 -G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be Ͼ1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated. selective breeding; exercise; genes; nucleus accumbens; RNA-seq APPROXIMATELY 97% OF US adults and 92% of adolescents are not meeting US daily physical activity guidelines for 30 and 60 min, respectively (44). The clinical significance of lack of sufficient daily physical activity is an increased prevalence of 35 chronic unhealthy conditions and premature death (5). Motivation, fitness, and genes are all associated with physical activity levels (4). Twin and family studies have shown that genetic factors contribute to variation in reported daily physical activity levels, with identical cotwins showing smaller intraindividual variation than nontwins (see Ref. 4 for references).Animal studies also suggest that brain mechanisms affect the quantity of daily voluntary running (14,21,22,36,38).One approach to obtain genetic information on genes and physical activity has been to employ a selective breeding model of physical activity in rodents. According to Rhodes et al. (35), selective breeding is a "powerful alternative" compared with knockout models in studying genotype-phenotype interactions, given that multiple genes contribute to complex phenotypes. Swallow et al. (42) have phenotyped their 10th generation of mice selected for the highest revolutions per day of wheel running, these being ...

Introduction-Absence of functional myostatin (MSTN) during fetal development results in adult skeletal muscle hypertrophy and hyperplasia.

Estrogen (E2) is reported to regulate skeletal muscle mass and contractile function; whether E2 exerts its effects through estrogen receptor-alpha (ERalpha) or -beta (ERbeta) is unclear. We determined the effect of ERalpha or ERbeta elimination on muscle mass and contractile function in multiple muscles of the lower limb, muscles with different locomotor tasks and proportions of fiber types I and II: soleus (Sol), plantaris (Plan), tibialis anterior (TA), and gastrocnemius (Gast) in mature female mice. To determine E2 elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ERalpha and ArKO body weights were approximately 10 and 20% higher than WT. Although muscle mass tended to show a commensurate increase in both groups, only the TA was significantly larger in ERalpha (P<0.05). Ratios of muscle mass to body mass revealed significantly lower values for Gast and TA in ArKO mice (P<0.05). Tetanic tension (Po) per calculated anatomical cross-sectional area (aCSA) in ERalpha KO was lower in TA and Gast than in WT. Lower Po/aCSA in ERalpha KO Gast and TA was also supported histologically by significantly less Po/fiber areas (P<0.05). ArKO mice also had lower Po/aCSA in Gast and TA compared with WT. ERbeta KO and WT mice were comparable in all measures. Our results support the hypothesis that E2 effects on skeletal muscle are mediated in part via the ERalpha but that E2 effects may be mediated via more than one mechanism or receptor.

The Morey-Holton hindlimb unloading (HU) method is a widely accepted National Aeronautics and Space Administration (NASA) ground-based model for studying disuse-atrophy in rodents [4][5][6] . Our study evaluated an alternant method to the gold-standard Morey-Holton HU tail-traction technique in mice. Fifty-four female mice (4-8 mo.) were HU for 14 days (n=34) or 28 days (n=20). Recovery from HU was assessed after 3 days of normal cage ambulation following HU (n=22). Aged matched mice (n=76) served as weight-bearing controls.Prior to HU a tail ring was formed with a 2-0 sterile surgical steel wire that was passed through the 5 th , 6 th , or 7 th inter-vertebral disc space and shaped into a ring from which the mice were suspended. Vertebral location for the tail-ring was selected to appropriately balance animal body weight without interfering with defecation.We determined the success of this novel HU technique by assessing body weight before and after HU, degree of soleus atrophy, and adrenal mass following HU. Body weight of the mice prior to HU (24.3 ± 2.9g) did not significantly decline immediately after 14d of HU (22.7 ± 1.9g), 28d of HU (21.3 + 2.1g) or after 3 days recovery (24.0 ± 1.8g). Soleus muscle mass significantly declined (-39.1%, and -46.6%) following HU for 14 days and 28 days respectively (p<0.001). Following 3 days of recovery soleus mass significantly increased to 74% of control values. Adrenal weights of HU mice were not different compared to control mice.The success of our novel HU method is evidenced by the maintenance of animal body weight, comparable adrenal gland weights, and soleus atrophy following HU, corresponding to expected literature values 2,7,8 . The primary advantages of this HU method include: 1) ease of tail examination during suspension; 2) decreased likelihood of cyanotic, inflamed, and/or necrotic tails frequently observed with tail-taping and HU; 3) no possibility of mice chewing the traction tape and coming out of the suspension apparatus; and 4) rapid recovery and normal cage activity immediately after HU.