Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy.

We describe a novel phenotype in mice lacking the major antioxidant enzyme, CuZn-superoxide dismutase (Sod1(-/-) mice), namely a dramatic acceleration of age-related loss of skeletal muscle mass. Sod1(-/-) mice are 17 to 20% smaller and have a significantly lower muscle mass than wild-type mice as early as 3 to 4 months of age. Muscle mass in the Sod1(-/-) mice is further reduced with age and by 20 months, the hind-limb muscle mass in Sod1(-/-) mice is nearly 50% lower than in age-matched wild-type mice. Skeletal muscle tissue from young Sod1(-/-) mice has elevated oxidative damage to proteins, lipids, and DNA compared to muscle from young wild-type mice. The reduction in muscle mass and elevated oxidative damage are accompanied by a 40% decrease in voluntary wheel running by 6 months of age and decreased performance on the Rota-rod test at 13 months of age, but are not associated with a decline in overall spontaneous activity. In some of the old Sod1(-/-) mice, the loss in muscle mass is also associated with the presence of tremors and gait disturbances. Thus, the absence of CuZnSOD imposes elevated oxidative stress, loss of muscle mass, and physiological consequences that resemble an acceleration of normal age-related sarcopenia.

Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating.

Although critical for transducing seasonal information, melatonin has also been implicated in several physiological systems, as well as the regulation of behavioral and cognitive processes. Therefore, we investigated the neurobehavioral effects of mice missing the type 1 melatonin receptor (MT1). Male and female MT1 knockout (MT1-/-) and wild-type (WT) mice were tested in the acoustic startle/prepulse inhibition (PPI), open field and Porsolt forced swim tests. Male and female MT1-/- mice displayed dramatically impaired prepulse inhibition in the acoustic startle response. Female WT mice were more active in the open field than WT males. However, male and female MT1-/- mice did not differ in total locomotor activity. WT animals spent significantly more time in the center of the arena (a behavioral outcome associated with reduced anxiety-like behavior) than MT1-/- mice. Also, the sex difference between male and female WT mice in the amount of time spent in the center versus periphery was not observed among MT1-/- mice. Both male and female MT1-/- mice significantly increased the time spent immobile in the forced swim test, an indication of depressed-like behavior. The lifetime lack of MT1 signaling contributes to behavioral abnormalities including impairments in sensorimotor gating and increases in depressive-like behaviors. Taken together, MT1 receptor signaling may be important for normal brain and behavioral function.

The use of behavioral test batteries, II: effect of test interval.

Test batteries are commonly used to assess the behavioral phenotype of genetically modified and inbred strains of mice. However, few systematic studies have been employed to address several key issues concerning the use of a test battery. The current study was designed to address whether inter-test interval affects behavioral performance. Male mice of 3 different inbred strains and one F1 hybrid strain were randomly assigned to either a test battery with 1 week inter-test intervals, or a rapid test battery with 1-2 day inter-test intervals. The test battery included a neurological exam, open-field activity, light-dark exploration, rotarod test, prepulse inhibition, and startle habituation. The experiment was repeated with female animals of 2 different strains. As expected, there were strain differences on each of the behavioral assays; however, there was no major difference in performance between mice of the standard test battery and the rapid test battery. Similar results were found with females. These results indicate that the interval between most tests could be as little as 1-2 days, with little significant effect on overall performance. Thus, it is possible with the current test battery to reduce the inter-test interval to facilitate the rate of studying and identifying behavioral phenotypes in mice.