The behavioural consequences of dystrophinopathy

Verhaeg, M.A.T.; Pijl, E.M. van der; Vijver, D. van de; Winter, C.L.T.D.; Stan, T.L.; Uffelen, A. van; Censoni, L.; Putten, M. van

doi:doi:10.1242/dmm.052047

Duchenne muscular dystrophy is a severe neuromuscular disorder, caused by mutations in the DMD gene. Normally, the DMD gene gives rise to many dystrophin isoforms, of which multiple are expressed in the brain. The location of the mutation determines the number of dystrophin isoforms affected, and the absence thereof leads to behavioral and cognitive impairments. Even though behavioral studies have thoroughly investigated the effects of the loss of Dp427, and to a lesser extent of Dp140, in mice, direct comparisons between models lacking multiple dystrophin isoforms are sparse. Furthermore, a behavioral characterization of the DMDnull mouse, which lacks all dystrophin isoforms, has never been undertaken. Using a wide variety of behavioral tests, we directly compared impairments between mdx5cv,mdx52 and DMD-null mice. We confirmed the role of Dp427 in emotional reactivity. We did not find any added effects of loss of Dp140 on fear, but showed the involvement of Dp140 in spontaneous...Show moreDuchenne muscular dystrophy is a severe neuromuscular disorder, caused by mutations in the DMD gene. Normally, the DMD gene gives rise to many dystrophin isoforms, of which multiple are expressed in the brain. The location of the mutation determines the number of dystrophin isoforms affected, and the absence thereof leads to behavioral and cognitive impairments. Even though behavioral studies have thoroughly investigated the effects of the loss of Dp427, and to a lesser extent of Dp140, in mice, direct comparisons between models lacking multiple dystrophin isoforms are sparse. Furthermore, a behavioral characterization of the DMDnull mouse, which lacks all dystrophin isoforms, has never been undertaken. Using a wide variety of behavioral tests, we directly compared impairments between mdx5cv,mdx52 and DMD-null mice. We confirmed the role of Dp427 in emotional reactivity. We did not find any added effects of loss of Dp140 on fear, but showed the involvement of Dp140 in spontaneous behavior, specifically in habituation and activity changes due to light/dark switches. Lastly, our results indicate that Dp71/Dp40 play an important role in many behavioral domains, including anxiety and spontaneous behavior.Show less

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The behavioural consequences of dystrophinopathy