Diversity of Human Clock Genotypes and Consequences - Progress in Molecular Biology and Translational Science - page 69

Figure 3.2 Activity recording of a DEC2-P384R mutation carrier. Filled bars indicate
periods of activity by wrist actigraphy. Extended periods of activity can be observed.
Adapted from Ref. 125 .
mice were generated to carry wild-type h DEC2 (h DEC2-WT) or h DEC2-
P384R .h DEC2-P384R mice do not exhibit altered free-running period,
but the duration of the activity period (alpha) is 1.2-h longer relative to
hDEC2-WT transgenic, wild-type littermates, and Dec2 knockout mice.
This recapitulates the shorter sleep duration (i.e., inactive period) phenotype
observed in humans. Moreover, when h DEC2-P384R is expressed in a
Dec2 knockout background, alpha is further lengthened to 2.5 h longer
than controls.
To examine the effects of the DEC2-P384R mutation on sleep, EEG
and electromyography were performed on mutant transgenic mice and lit-
termate controls. h DEC2-P384R mice were awake for a significantly longer
period of time during the light phase compared to wild type, accompanied
by significant reduction of both NREM and REM sleep. Analysis of sleep
architecture demonstrated decreased wake duration and an increase in the
number of wake episodes in h DEC2-P384R mice relative to wild type.
In addition, these animals exhibited significantly more NREM episodes dur-
ing the light phase, but each episode is shorter in duration. These results
indicate that sleep (in particular NREM sleep) is more fragmented in
h DEC2-P384R mice than that of wild type. To better understand the role
of DEC2 in sleep regulation, h DEC2-P384R mice and wild-type littermates
were subjected to acute sleep deprivation. h DEC2-P384R mice showed sig-
nificantly less rebound in both NREM and REM sleep, and a slower recov-
ery of acute sleep loss. h DEC2-P384R mice also exhibited lower NREM