Sleep-like behavior and 24 hour rhythm disruption in the Tc1 mouse model of Down syndrome.

Journal article

Down syndrome is a common disorder associated with intellectual disability in humans. Amongst a variety of severe health problems, patients with Down syndrome exhibit disrupted sleep and abnormal 24 h rest/activity patterns. The transchromosomic mouse model of Down syndrome, Tc1, is a trans-species mouse model for Down syndrome, carrying most of human chromosome 21 in addition to the normal complement of mouse chromosomes and expresses many of the phenotypes characteristic of Down syndrome. To date, however, sleep and circadian rhythms have not been characterised in Tc1 mice. Using both circadian wheel running analysis and video-based sleep scoring we show that these mice exhibited fragmented patterns of sleep-like behavior during the light phase of a 12:12 h light:dark cycle with an extended period of continuous wakefulness at the beginning of the dark phase. Moreover, an acute light pulse during night time was less effective in inducing sleep-like behavior in Tc1 animals than in wild-type controls. In wheel-running analysis, free running in constant light or constant darkness revealed no changes in the circadian period of Tc1 animals although they did express subtle behavioural differences including a reduction in total distance travelled on the wheel and differences in the acrophase of activity in light:dark and in constant darkness. Our data confirm that Tc1 mice express sleep-related phenotypes that are comparable to those seen in Down syndrome patients with moderate disruptions in rest/activity patterns and hyperactive episodes while circadian period under constant lighting conditions is essentially unaffected.

Authors: Heise, I; Fisher, S; Banks, G; Wells, S; Peirson, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Genes, Brain and Behavior
• Volume: 14
• Issue: 2
• Pages: 209–216
• Publication date: 2015-02-01
• DOI: 10.1111/gbb.12198
• EISSN: 1601-183X
• ISSN: 1601-1848
• Language: English
• Keywords: Tc1; sleep; circadian wheel running; trans-species aneuploid mouse line; Down syndrome