Substrains of inbred mice differ in their physical activity as a behavior

Abstract

Recent studies strengthen the belief that physical activity as a behavior has a genetic basis. Screening wheel-running behavior in inbred mouse strains highlighted differences among strains, showing that even very limited genetic differences deeply affect mouse behavior. We extended this observation to substrains of the same inbred mouse strain, that is, BALB/c mice. We found that only a minority of the population of one of these substrains, the BALB/c J, performs spontaneous physical activity. In addition, the runners of this substrain cover a significantly smaller distance than the average runners of two other substrains, namely, the BALB/c ByJ and the BALB/c AnNCrl. The latter shows a striking level of voluntary activity, with the average distance run/day reaching up to about 12 kilometers. These runners are not outstanders, but they represent the majority of the population, with important scientific and economic fallouts to be taken into account during experimental planning. Spontaneous activity persists in pathological conditions, such as cancer-associated cachexia. This important amount of physical activity results in a minor muscle adaptation to endurance exercise over a three-week period; indeed, only a nonsignificant increase in NADH transferase+ fibers occurs in this time frame.

Figure 1

Different mouse substrains show differential physical activity as a behavior. Seven-week-old female BALB/c mice, belonging to three different substrains as indicated, were individually placed in wheel equipped cages. The running behavior (a) and the daily distance covered (b) were recorded for four days. The average ± SEM of at least three independent experiments, each one performed at least in quadruplicate, is shown. BALB/c J mice run significantly less than the other two substrains and the majority of this population do not show at all interest for wheel running. (a) *P < 0.01 by Tukey HSD test versus AnNCrl or versus ByJ. (b) *P < 0.05 by Sutdent's t-test versus AnNCrl.

Figure 2

Kinetics of physical activity in healthy and C26-bearing BALB/c AnNCrl mice. Seven-week-old female BALB/c AnNCrl mice were individually placed in wheel equipped cages. At the same time a group (C26 bearing) was subcutaneously transplanted with the C26 colon carcinoma to induce muscle wasting. The running distance was daily recorded and averaged among replicates from at least three independent experiments. Both healthy and diseased mice do exercise, even though C26-bearing mice run for up to 6 Km/day, while healthy mice increased the daily distance run on the wheel to 11 Km/day. *P < 0.01 by Tukey's HSD test versus C26-bearing mice.

Figure 3

Muscle metabolic adaptations to wheel running in BALB/c AnNCrl mice. Histochemistry for NADH transferase activity highlights oxidative (O), intermediate (I), and glycolytic (G) fibers; that is, muscle fibers that are rich (O or I) and poor in mitochondrial content, respectively. The inset at higher magnification allows to differentiate among the three types of fibers. O + I fibers were collectively considered as rich in NADH transferase (NADH-TR  + fibers). Representative photomicrographs of the TA of (a) control, nonexercised mouse and (b) a mouse following nineteen days of exercise. The percentage of NADH-TR+ fibers was quantified in replicate, after no (0), five (5), or nineteen (19) days of wheel running.