Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.

The various functions of skeletal muscle (movement, respiration, thermogenesis, etc.) require the presence of oxygen (O2). Inadequate O2 bioavailability (ie, hypoxia) is detrimental to muscle function and, in chronic cases, can result in muscle wasting. Current therapeutic interventions have proven largely ineffective to rescue skeletal muscle from hypoxic damage. However, our lab has identified a mammalian skeletal muscle that maintains proper physiological function in an environment depleted of O2. Using mouse models of in vivo hindlimb ischemia and ex vivo anoxia exposure, we observed the preservation of force production in the flexor digitorum brevis (FDB), while in contrast the extensor digitorum longus (EDL) and soleus muscles suffered loss of force output. Unlike other muscles, we found that the FDB phenotype is not dependent on mitochondria, which partially explains the hypoxia resistance. Muscle proteomes were interrogated using a discovery-based approach, which identified significantly greater expression of the transmembrane glucose transporter GLUT1 in the FDB as compared to the EDL and soleus. Through loss-and-gain-of-function approaches, we determined that GLUT1 is necessary for the FDB to survive hypoxia, but overexpression of GLUT1 was insufficient to rescue other skeletal muscles from hypoxic damage. Collectively, the data demonstrate that the FDB is uniquely resistant to hypoxic insults. Defining the mechanisms that explain the phenotype may provide insight towards developing approaches for preventing hypoxia-induced tissue damage.

Isometric skeletal muscle contractile properties in common strains of male laboratory mice.

Assessing contractile function of skeletal muscle in murine models is a commonly employed laboratory technique that investigators utilize to measure the impact of genetic manipulations, drug efficacy, or other therapeutic interventions. Often overlooked is the potential for the strain of the mouse to influence the functional properties of the skeletal muscle. Thus, we sought to characterize commonly assessed isometric force measures in the hindlimb muscles across a variety of mouse strains. Using 6-8-week-old male mice, we measured isometric force, fatigue susceptibility, relaxation kinetics, muscle mass, myofiber cross-sectional area, and fiber type composition of the extensor digitorum longus (EDL) and soleus muscles in C57BL/6NJ, BALB/cJ, FVB/NJ, C57BL/6J, and C57BL/10 mice. The data demonstrate both unique differences and a number of similarities between both muscles in the various genetic backgrounds of mice. Soleus muscle specific force (i.e., force per unit size) exhibited higher variation across strains while specific force of the EDL muscle exhibited minimal variation. In contrast, absolute force differed only in a few mouse strains whereas analysis of muscle morphology revealed many distinctions when compared across all the groups. Collectively, the data suggest that the strain of the mouse can potentially influence the measured biological outcome and may possibly promote a synergistic effect with any genetic manipulation or therapeutic intervention. Thus, it is critical for the investigator to carefully consider the genetic background of the mouse used in the experimental design and precisely document the strain of mouse employed during publication.