Summary
MOP3 (also known as BMAL1), a master regulator of circadian rhythm, plays important roles in the regulation of cell differentiation and general physical functions. In the present studies, MOP3 deficient mice had significantly reduced body weight and showed remarkable mortality around six months of age. The levels of AST, ALT, BUN, or UREA in the blood of about four month-old MOP3−/− mice were significantly higher than MOP3+/− or MOP3+/+ littermates. However, no apparent pathological changes in the livers, hearts, lungs or kidneys of about four month-old MOP3−/− mice were observed. In addition, altered levels of white blood cells, lympgocytes, and platelets in peripheral blood of MOP3−/−mice were detected. The results presented herein with MOP3-deficient mice offered the basic principle for the essential roles of MOP3 in keeping normal survival abilities in mice. This study may have significant clinical impacts on the consideration about the abnormality of circadian rhythms and sleeping disorders caused physical and metabolism dysfunctions as well as the mortality.
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Abbreviations
- ALT:
-
alanine aminotransferase
- ARNT:
-
aryl hydrocarbon receptor nuclear translocator
- AST:
-
asparate aminotransferase
- bHLH:
-
basic-helix-loop-helix domain
- BMAL1:
-
brain and muscle Arnt-like protein-1
- CLOCK:
-
product of the clock locus in mice
- HIF:
-
hypoxia-inducible factor
- PAS:
-
PER-ARNT-SIM homology domain
- SGPT:
-
serum glutamic pyruvic transaminase
- SGOT:
-
serum glutamic oxalocetic transaminase
References
Hankinson O., Brooks B.A., Weir-Brown K.I., Hoffman E.C., Johnson B.S., Nanthur J., Reyes H., Watson A.J., Genetic and molecular analysis of the Ah receptor and of Cyp1a1 gene expression. Biochimie. 73:61–66, 1991
Burbach K.M., Poland A., Bradfield C.A., Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. USA 89:8185–8189, 1992
King D.P., Zhao Y., Sangoram A.M., Wilsbacher L.D., Tanaka M., Antoch M.P., Steeves T.D., Vitaterna M.H., Kornhauser J.M., Lowrey P.L., et al., Positional cloning of the mouse circadian clock gene. Cell 89:641–653, 1997
Bunger M.K., Wilsbacher L.D., Moran S.M., Clendenin C., Radcliffe L.A., Hogenesch J.B., Simon M.C., Takahashi J.S., Bradfield C.A., Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103:1009–1017, 2000
Hogenesch J.B., Gu Y.Z., Jain S., Bradfield C.A., The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc. Natl. Acad. Sci. USA 95:5474–5479, 1998
Matsuo T., Yamaguchi S., Mitsui S., Emi A., Shimoda F., Okamura H., Control mechanism of the circadian clock for timing of cell division in vivo. Science 302:255–259, 2003
Shimba S., Ishii N., Ohta Y., Ohno T., Watabe Y., Hayashi M., Wada T., Aoyagi T., Tezuka M., Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc. Natl. Acad. Sci. USA 102:12071–12076, 2005
Rudic R.D., McNamara P, Curtis A.M., Boston R.C., Panda S., Hogenesch J.B., Fitzgerald G.A., BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS. Biol. 2:e377, 2004
Turek F.W., Joshu C., Kohsaka A., Lin E., Ivanova G., McDearmon E., Laposky A., Losee-Olson S., Easton A., Jensen D.R. et al., Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308:1043–1045, 2005
Munoz E., Brewer M., Baler R., Circadian Transcription. Thinking outside the E-Box. J. Biol. Chem. 277:36009–36017, 2002
Pennathur-Das R., Levitt L., Augmentation of in vitro human marrow erythropoiesis under physiological oxygen tensions is mediated by monocytes and T lymphocytes. Blood 69:899–907, 1987
Acknowledgements
We thank Dr. Guangwei Liu for his review of the manuscript. This work was supported by grants from the Knowledge Innovation Program of Chinese Academy of Sciences (KSCX2-SW-333), 100 Quality Vocational Colleagues of Chinese Academy of Sciences (2003), National Science Fund for Distinguished Young Scholar, National Natural Science Foundation of China (C03020504), the National Basic Research Program (973 Program, 2003CB515501), the Scientific Research Foundation for the Returned Overseas Chinese Scholars of State Education Ministry (2005–546, Y.Z.), and Nebraska Department of Health and Human Services.
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Sun, Y., Yang, Z., Niu, Z. et al. The mortality of MOP3 deficient mice with a systemic functional failure. J Biomed Sci 13, 845–851 (2006). https://doi.org/10.1007/s11373-006-9108-4
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DOI: https://doi.org/10.1007/s11373-006-9108-4