title: Cognitive flexibility deficits in a mouse model for the absence of full-length dystrophin.
abstract: Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder, caused by mutations in the DMD gene and the resulting lack of dystrophin. The DMD gene has seven promoters, giving rise to multiple full-length and shorter isoforms. Besides the expression of dystrophin in muscles, the majority of dystrophin isoforms is expressed in brain and dystrophinopathy can lead to cognitive deficits, including intellectual impairments and deficits in executive function. In contrast to the muscle pathology, the impact of the lack of dystrophin on the brain is not very well studied. Here, we study the behavioral consequences of a lack of full-length dystrophin isoforms in mdx mice, particularly with regard to domains of executive functions and anxiety. We observed a deficit in cognitive flexibility in mdx mice in the absence of motor dysfunction or general learning impairments using two independent behavioral tests. In addition, increased anxiety was observed, but its expression depended on the context. Overall, these results suggest that the absence of full-length dystrophin in mice has specific behavioral effects that compare well to deficits observed in DMD patients.
authors.affiliation: Sylics (Synaptologics B.V.), The Netherlands.|Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, The Netherlands.|Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Remmelink
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Aartsma-Rus
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Sylics (Synaptologics B.V.), The Netherlands.
authors.forename: M
authors.identifier: 0000-0003-1629-2928
authors.initials: M
authors.lastname: Loos
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Putten
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D060825:Cognitive Dysfunction / Q000235:genetics*; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx
chemical_list: D016189:Dystrophin
keywords: Anxiety; Duchenne muscular dystrophy; automated home-cage; cognition; cognitive flexibility; mdx; mouse model; reversal learning