Changes in Object Recognition and Anxiety-Like Behaviour in Mice Expressing a Cx47 Mutation That Causes Pelizaeus-Merzbacher-Like Disease

Abstract

Pelizaeus-Merzbacher-like disease is characterized by impaired psychomotor development, ataxia, progressive spasticity and mental retardation. It is induced by mutations in the gap junction gene GJC2 that encodes for the gap junction protein connexin 47. Mice bearing a human Cx47M283T missense mutation have been generated as a transgenic mouse model of Pelizaeus-Merzbacher-like disease. Homozygous expression of the mutant connexin 47 gene in oligodendrocytes resulted in a complex and variable neuropathologic phenotype, which was associated with impairments in motor coordination in juvenile, but not adult mice. In the present study, we have investigated anxiety-like behaviour and spatial working memory in juvenile (P23) and adult (3-month-old) Cx47M282T mutant mice. Adult Cx47M282T mice were also evaluated in terms of neuromotor functions and in the novel object recognition test. Juvenile Cx47M282T mutant mice exhibited an increase in anxiety-like behaviour in the open field test, but no changes in spatial working memory performance. No significant changes in anxiety-like behaviour, spatial working memory or neuromotor functions were observed in the adult Cx47M282T mutant mice. However, novel object recognition was significantly impaired in adult Cx47M282T mice. Our results suggest that the expression of the human Cx47M282T mutation in the mouse causes changes in anxiety-like behaviour in juvenile and novel object recognition impairments in adult mice. It appears that the distortion of panglial gap junction coupling in white and grey matter tissue in the Cx47M282T mice is associated with a complex age-dependent behavioural phenotype including changes in psychomotor, emotional and memory functions.

Ablation of Neuronal Ceramide Synthase 1 in Mice Decreases Ganglioside Levels and Expression of Myelin-associated Glycoprotein in Oligodendrocytes

“…The time the mouse needed to reach one of the platforms was recorded during two trials with an intertrial interval of 30 -45 min. Horizontal wire test performance (see supplemental Table S1) was scored as described previously (35). A trial was terminated after an animal reached one of the platforms or if 180 s had elapsed.…”

Inactivation of Ceramide Synthase 6 in Mice Results in an Altered Sphingolipid Metabolism and Behavioral Abnormalities

“…Horizontal Wire Test-Mice were subjected to the horizontal wire test according to a previously described procedure (37). Briefly, 6-month-old CerS6KO and wild type mice were lifted up by their tail and allowed to grasp in the middle of a horizontally clamped wire (1 meter) that connected two platforms.…”

“…The animals were allowed to reach one of the platforms and climb onto it. Each animal was subjected twice to the horizontal wire test (with an inter-trial interval of 30 -45 min) and the performance of the animal was scored by an observer blind to the genotype by using a recently developed scoring system (37). Additionally, the time spent on the horizontal wire was measured for each trial.…”

Channels to consciousness: a possible role of gap junctions in consciousness

“…Transgenic mice bearing a human Cx47M282T missense mutation derived from patients with Pelizaeus-Merzbacher-like disease exhibited an 80% reduction in the number of cells participating in glial networks in the corpus callosum along with increased anxiety-like behavior in a novel environment and impaired rotarod performance at adolescent ages (Tress et al 2011;Zlomuzica et al 2012b). When tested in the adult stage, Cx47M282T mice showed impaired novel object recognition (Zlomuzica et al 2012c).…”