Figure 4. Behavioral rhythms are disrupted in β-Trcp1/2 mutant mice in a gene-dosage dependent manner.

(A) Representative actograms from β-Trcp1^+/-; β-Trcp2 ^fl/f / CAG-CreER-1 (n=3) and β-Trcp1 ^-/- ; β-Trcp2 ^fl/fl / CAG-CreER-1 (n=10) mutant mice. The arrow and shaded area indicate the LD to DD transfer and TM treatment, respectively. Locomotor activity was measured until the mutant mice died. (B) Quantification of period before and after TM treatment. (C) β-Trcp1^+/-; β-Trcp2^-/+ and β-Trcp1^-/-; β-Trcp2^-/+ mutant mice exhibit slightly longer periods than matching wt mice. The β-Trcp2 null allele (β-Trcp2^{knockout-First}) was used to generate the mutant mice. (D) Peripheral clocks are arrhythmic in β-Trcp1/2 double mutant mice. Wt and ko PER1 results were spliced from the same blots. (E) β-TRCP2 is almost absent 5 days after TM treatment. The mutant liver tissues from (D) were used. (F) Brain-specific β-Trcp2 mutant mice survived longer but exhibited similarly disrupted behavioral rhythms. Doxycycline (dox) in drinking water suppresses recombination in these mice [12].