Does genetic variation in titin affect mouse locomotion


Meeting Abstract

50.4  Thursday, Jan. 6  Does genetic variation in titin affect mouse locomotion? PACE, CM*; MONROY, JM; METOYER, A; ALDRIDGE, C; WANG, J; NISHIKAWA, KC; Northern Arizona University; Northern Arizona University; Northern Arizona University; Northern Arizona University; Northern Arizona University; Northern Arizona University Cinnamon.Pace@nau.edu

The protein titin is known to contribute to the elastic properties of skeletal muscle. To study titin’s contribution to muscle function and movement we used a mouse model (muscular dystrophy with myositis, mdm). Mdm mice have a deletion in the N2A region of their titin protein. By twelve days of age, homozygous mutant mice differ in size and gait from wild type and heterozygous mice, but heterozygous and wild type mice are superficially indistinguishable. Previous studies found no differences between genotypes in muscle contractile properties, although a recent study suggested subtle differences in locomotion between heterozygous and wild type mice. In addition, our recent work has shown that all three mdm genotypes vary in passive and active elasticity of the soleus muscle. The goal of this project was to determine whether mdm genotypes differ in their locomotor pattern. Homozygous mutant mice, heterozygous mice, and wild type mice were filmed walking using a high-speed digital imaging system. Differences in gait timing parameters of the left hindlimb were found among genotypes. Stride duty factor was smallest and swing phase duration was greatest in mutants. Values for heterozygotes were intermediate to the mutant and wild type mice. In addition, heterozygotes lifted their heel higher off the substrate during swing than wild type mice. We suggest that these differences in locomotion among mdm genotypes are due to titin-based differences in passive and active muscle elasticity. By combining whole animal locomotion studies with in vitro muscle studies, we will broaden our understanding on how titin contributes to muscle function and movement. Supported by NSF IOS-1025806

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