Forced Running Endurance Is Influenced by Gene(s) on Mouse Chromosome 10

Abstract

Phenotypic diversity between laboratory mouse strains provides a model for studying the underlying genetic mechanisms. The A/J strain performs poorly in various endurance exercise models. The aim of the study was to test if endurance capacity and contractility of the fast- and slow-twitch muscles are affected by the genes on mouse chromosome 10. The C57BL/6J (B6) strain and C57BL/6J-Chr 10A/J/NaJ (B6.A10) consomic strain which carries the A/J chromosome 10 on a B6 strain background were compared. The B6.A10 mice compared to B6 were larger in body weight (p < 0.02): 27.2 ± 1.9 vs. 23.8 ± 2.7 and 23.4 ± 1.9 vs. 22.9 ± 2.3 g, for males and females, respectively, and in male soleus weight (p < 0.02): 9.7 ± 0.4 vs. 8.6 ± 0.9 mg. In the forced running test the B6.A10 mice completed only 64% of the B6 covered distance (p < 0.0001). However, there was no difference in voluntary wheel running (p = 0.6) or in fatigability of isolated soleus (p = 0.24) or extensor digitorum longus (EDL, p = 0.7) muscles. We conclude that chromosome 10 of the A/J strain contributes to reduced endurance performance. We also discuss physiological mechanisms and methodological aspects relevant to interpretation of these findings.

Metabolism Analysis in Mice With Reduced Citrate Synthase Activity

“…CS activity depends on many metabolism processes and can be increased, for instance, by respiratory muscle training or during endurance exercise training (Holloszy & Booth, 1976;Jaenisch, Bertagnolli, Borghi-Silva, Arena, & Lago, 2017). Our recent studies showed similar results: mice with reduced CS activity had substantially lower endurance capacity compared to control mice with no sex effect on endurance performance (Kvedaras et al, 2017). These facts suggest that variation in CS activity may influence metabolic changes.…”

“…One possible explanation could be different type of mutation in chromosome 10, where Cs gene is localized in mouse model (Johnson, Gagnon, Longo-Guess, & Kane, 2012). In B6.A strain there is a missense mutation in Cs gene, while in B6.A10 whole chromosome 10 is substituted by homologous chromosome (Kvedaras et al, 2017). Therefore we could speculate that other genes in chromosome 10 could affect EE in B6.A10 mice with no association with reduced CS enzyme activity.…”

“…For metabolism experiment 16 week-old mice were chosen: control C57BL/6J (B6) mice with normal CS activity, B6.A-(rs3676616-D10Utsw1)/Kjn (B6.A) mice, carrying H55N polymorphism which is associated with reduced CS activity (Ratkevicius et al, 2010) and C57BL/6J-Chr 10A/J/NaJ (B6.A10) mice, carrying A/J chromosome 10 of B6 mice, this substitution is also associated with reduced citrate synthase activity (Kvedaras et al, 2017). Both male (n = 9 for each strain) and female (n = 9 for each strain) mice were studied.…”

Effects of Single 48 H Fasting on Soleus Muscle Mass and Contractile Properties in Old and Young Mice

“…At the end of the intervention mice were sacrificed by the exposure to CO 2 . Immediately afterwards, as in our previous study, SOL muscle was dissected and weighed (Kvedaras et al, 2017).…”

“…Muscle contractile properties. Force output of SOL muscle was assessed in vitro using muscle test system (1200A-LR Muscle Test System, Aurora Scientific Inc., Canada) as in our previous study (Kvedaras et al, 2017). For these measurements, muscles were placed between two platinum electrodes in Tyrode solution (121 mM NaCl, 5 mM KCl, 0.5 mM MgCl 2 , 1.8 mM CaCl 2 , 0.4 mM NaH 2 PO 4 , 0.1 mM NaEDTA, 24 mM NaHCO 3 , 5.5 mM glucose) which was bubbled with a gas mixture of 95% O 2 and 5% CO 2 at pH 7.4 and ~22˚C.…”