AUTHOR=Lee Frank Y. , Wang Huei-Bin , Hitchcock Olivia N. , Loh Dawn Hsiao , Whittaker Daniel S. , Kim Yoon-Sik , Aiken Achilles , Kokikian Collette , Dell’Angelica Esteban C. , Colwell Christopher S. , Ghiani Cristina A. TITLE=Sleep/Wake Disruption in a Mouse Model of BLOC-1 Deficiency JOURNAL=Frontiers in Neuroscience VOLUME=12 YEAR=2018 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00759 DOI=10.3389/fnins.2018.00759 ISSN=1662-453X ABSTRACT=
Mice lacking a functional Biogenesis of Lysosome-related Organelles Complex 1 (BLOC-1), such as those of the pallid line, display cognitive and behavioural impairments reminiscent of those presented by individuals with intellectual and developmental disabilities. Although disturbances in the sleep/wake cycle are commonly lamented by these individuals, the underlying mechanisms, including the possible role of the circadian timing system, are still unknown. In this paper, we have explored sleep/circadian malfunctions and underlying mechanisms in BLOC-1-deficient pallid mice. These mutants exhibited less sleep behaviour in the beginning of the resting phase than wild-type mice with a more broken sleeping pattern in normal light-dark conditions. Furthermore, the strength of the activity rhythms in the mutants were reduced with significantly more fragmentation and lower precision than in age-matched controls. These symptoms were accompanied by an abnormal preference for the open arm in the elevated plus maze in the day and poor performance in the novel object recognition at night. At the level of the central circadian clock (the suprachiasmatic nucleus, SCN), loss of BLOC-1 caused subtle morphological changes including a larger SCN and increased expression of the relative levels of the clock gene