Loss of circadian rhythmicity in aging mPer1-/-mCry2-/- mutant mice.
The mPer1, mPer2, mCry1, and mCry2 genes play a central role in the molecular mechanism driving the central pacemaker of the mammalian circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In vitro studies suggest a close interaction of all mPER and mCRY proteins. We investigated mPER and mCRY interactions in vivo by generating different combinations of mPer/mCry double-mutant mice. We previously showed that mCry2 acts as a nonallelic suppressor of mPer2 in the core clock mechanism. Here, we focus on the circadian phenotypes of mPer1/mCry double-mutant animals and find a decay of the clock with age in mPer1-/- mCry2-/- mice at the behavioral and the molecular levels. Our findings indicate that complexes consisting of different combinations of mPER and mCRY proteins are not redundant in vivo and have different potentials in transcriptional regulation in the system of autoregulatory feedback loops driving the circadian clock.
Oster
Henrik
H
Department of Medicine, Division of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland.
Baeriswyl
Stephanie
S
Van Der Horst
Gijsbertus T J
GT
Albrecht
Urs
U
D000375:Aging / Q000235:genetics*; D000818:Animals; D001683:Biological Clocks; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D003433:Crosses, Genetic; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005260:Female; D005420:Flavoproteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007031:Hypothalamus / Q000254:growth & development / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D056950:Period Circadian Proteins; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled; D013493:Suprachiasmatic Nucleus / Q000254:growth & development / Q000502:physiology
D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D043562:Receptors, G-Protein-Coupled; C119828:cry protein, Drosophila