Differences In Msra And Mtmr9 Protein Expression In High- And Low-active Mouse Strains

In preliminary studies we found two genes, Msra and Mtmr9, trending towards higher expression in the soleus of low-active C3H/HeJmice as compared to high-active C57BL/6J mouse strains. Msra encodes the methionine sulfoxide A protein and plays a role in reducing the effects of oxidative stress by regulating the conversion of methionine sulfoxide to methionine. Mtmr9 encodes myotubulin related protein 9 which regulates inositol tri-phosphate (IP3) function, thus aiding in the regulation of intracellular calcium ion (Ca++) concentration. PURPOSE: To compare Msra and Mtmr9 protein expression between C57BL/6J (high-active) and C3H/HEJ (low-active) inbred mouse strains in skeletal muscle and brain tissue. METHODS: To test for differences in expression, we used 8-week old mice C57BL/6J (n=12, 6 male and 6 female) and C3H/HeJ (n=12, 6 male and 6 female) mice (Jackson Laboratories) and allowed them to acclimate for a period of 1-week. Then, Msra and Mtmr9 protein expression were assayed in the gastrocnemius, soleus, and nucleus accumbens using western blot techniques. RESULTS: There was significantly lower between-strain Msra expression in the nucleus accumbens of C57BL/6J mice (p=0.04). Only male C57BL/6J exhibited significantly lower Msra expression in the nucleus accumbens compared to male C3H/HeJ mice (p=0.0008). Significant difference in skeletal muscle Msra expression was seen only in soleus tissue, with male C57BL/6J mice having higher expression (p=0.003). High-active female mice (C57Bl/6J) showed a lower expression of Mtmr9 in the soleus compared to female C3H/HeJ mice (p=0.03). CONCLUSIONS: Considering Mtmr9 expression was not influenced by spontaneous activity, strain, or tissue, we conclude that Mtmr9 is not associated with regulation of spontaneous physical activity level. However, results show sex differences in Msra expression between high- and low-active animals. Further, the tissue differences in Msra expression by activity level suggest that care must be taken when interpreting whole body RNA- or protein-expression differences. Since whole-body knockout models of Msra were shown to ambulate significantly less than wildtype mice, it is still unclear whether skeletal muscle or brain Msra expression plays a role in regulating spontaneous physical activity level. Funding: Study funding from the Texas A&M Institute for Advanced Studies.