TY - JOUR
T1 - Pleiotropic effects of cryptoChromes 1 and 2 on free-running and light-entrained murine circadian rhythms
AU - Van Gelder, Russell N.
AU - Gibler, Therese M.
AU - Tu, Daniel
AU - Embry, Kris
AU - Selby, Christopher P.
AU - Thompson, Carol L.
AU - Sancar, Aziz
N1 - Funding Information:
RNVG was supported by a Research to Prevent Blindness Career Development Award, the Becker/AUPO/RPB Physician-Scientist Award, the Horncrest Foundation, and NIH EYK08-00403. DT was supported by a Fight for Sight student research fellowship. AS was supported by NIH grant GM31082. We thank Drs. Ignacio Provencio and Ana Maria Castrucci of Uniformed Services University of Health Sciences for performing the melanopsin antibody staining. The authors thank Dr. Lynn Enquist for providing GFP-Bartha PRV-152, and Dr. David Leib for assistance with viral titration.
PY - 2002/7
Y1 - 2002/7
N2 - Cryptochromes function in both light entrainment of circadian rhythms and in a peripheral circadian clock mechanism in Drosophila. Mice have two closely related cryptochrome genes (mCry1 and mCry2). To further understand the roles of mammalian cryptochromes, we bred mice to carry all possible combinations of wild-type and cryptochrome knockout alleles, and tested these mice for free-running and entrained circadian rhythmicity. We find that a single wild-type copy of mCry1, but not mCry2, is sufficient for free running circadian rhythmicity; however, these mice show markedly variable free-running periods. Two wild-type copies of either mCry1 or mCry2 are sufficient to establish a stable free-running clock. A subset of mCry1-/mCry-; mCry2-/mCry2- mice have a diurnal activity preference, suggesting that cryptochromes function in light-dependent behavioral masking. We also analyzed mice lacking both cryptochromes and carrying the homozygous rd retinal degeneration mutation. These mice have markedly depressed behavioral photoresponses in light-dark conditions, despite having an anatomically intact retinohypothalamic tract and normal expression of melanopsin. These results suggest that, similar to insect cryptochromes, mammalian cryptochromes function pleiotropically in both circadian rhythm generation and in photic entrainment and behavioral responses.
AB - Cryptochromes function in both light entrainment of circadian rhythms and in a peripheral circadian clock mechanism in Drosophila. Mice have two closely related cryptochrome genes (mCry1 and mCry2). To further understand the roles of mammalian cryptochromes, we bred mice to carry all possible combinations of wild-type and cryptochrome knockout alleles, and tested these mice for free-running and entrained circadian rhythmicity. We find that a single wild-type copy of mCry1, but not mCry2, is sufficient for free running circadian rhythmicity; however, these mice show markedly variable free-running periods. Two wild-type copies of either mCry1 or mCry2 are sufficient to establish a stable free-running clock. A subset of mCry1-/mCry-; mCry2-/mCry2- mice have a diurnal activity preference, suggesting that cryptochromes function in light-dependent behavioral masking. We also analyzed mice lacking both cryptochromes and carrying the homozygous rd retinal degeneration mutation. These mice have markedly depressed behavioral photoresponses in light-dark conditions, despite having an anatomically intact retinohypothalamic tract and normal expression of melanopsin. These results suggest that, similar to insect cryptochromes, mammalian cryptochromes function pleiotropically in both circadian rhythm generation and in photic entrainment and behavioral responses.
KW - Circadian rhythms
KW - Cryptochrome
KW - Entrainment
KW - Masking
KW - Retinal degeneration
KW - Retinohypothalamic tract
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U2 - 10.1080/01677060215306
DO - 10.1080/01677060215306
M3 - Article
C2 - 12696673
AN - SCOPUS:0036665022
SN - 0167-7063
VL - 16
SP - 181
EP - 203
JO - Journal of Neurogenetics
JF - Journal of Neurogenetics
IS - 3
ER -