Generation of myometrium-specific Bmal1 knockout mice for parturition analysis
Christine K. Ratajczak A , Minoru Asada B , Gregg C. Allen C , Douglas G. McMahon C , Lisa M. Muglia D , Donté Smith D , Sandip Bhattacharyya D and Louis J. Muglia D E
+ Author Affiliations
- Author Affiliations
A Molecular Cell Biology Program, Washington University, St Louis, MO 63110, USA.
B Department of Pediatrics, Washington University, St Louis, MO 63110, USA.
C Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
D Departments of Molecular Physiology and Biophysics and Pediatrics, Vanderbilt University School of Medicine and the Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN 37232, USA.
E Corresponding author. Email: louis.muglia@vanderbilt.edu
Reproduction, Fertility and Development 24(5) 759-767 https://doi.org/10.1071/RD11164
Submitted: 24 June 2011 Accepted: 29 November 2011 Published: 6 January 2012
Abstract
Human and rodent studies indicate a role for circadian rhythmicity and associated clock gene expression in supporting normal parturition. The importance of clock gene expression in tissues besides the suprachiasmatic nucleus is emerging. Here, a Bmal1 conditional knockout mouse line and a novel Cre transgenic mouse line were used to examine the role of myometrial Bmal1 in parturition. Ninety-two percent (22/24) of control females but only 64% (14/22) of females with disrupted myometrial Bmal1 completed parturition during the expected time window of 5 p.m. on Day 19 through to 9 a.m. on Day 19.5 of gestation. However, neither serum progesterone levels nor uterine transcript expression of the contractile-associated proteins Connexin43 and Oxytocin receptor differed between females with disrupted myometrial Bmal1 and controls during late gestation. The data indicate a role for myometrial Bmal1 in maintaining normal time of day of parturition.
Additional keywords: circadian rhythm, genetics, pregnancy, preterm labour, smooth muscle.
References
Alvarez, J. D., Hansen, A., Ord, T., Bebas, P., Chappell, P. E., Giebultowicz, J. M., Williams, C., Moss, S., and Sehgal, A. (2008). The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice. J. Biol. Rhythms 23, 26–36.| The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXit1Ckurs%3D&md5=a0d53decabb92592e80b82eceee7df08CAS | 18258755PubMed |
Antoch, M. P., Song, E. J., Chang, A. M., Vitaterna, M. H., Zhao, Y., Wilsbacher, L. D., Sangoram, A. M., King, D. P., Pinto, L. H., and Takahashi, J. S. (1997). Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89, 655–667.
| Functional identification of the mouse circadian Clock gene by transgenic BAC rescue.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXjsVSmtL4%3D&md5=b0ed9939011f11520fe1620b63ac9a35CAS | 9160756PubMed |
Bunger, M. K., Wilsbacher, L. D., Moran, S. M., Clendenin, C., Radcliffe, L. A., Hogenesch, J. B., Simon, M. C., Takahashi, J. S., and Bradfield, C. A. (2000). Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103, 1009–1017.
| Mop3 is an essential component of the master circadian pacemaker in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXit1WrtQ%3D%3D&md5=b9b09fdda30f446495469b21df975f78CAS | 11163178PubMed |
Chappell, P. E., White, R. S., and Mellon, P. L. (2003). Circadian gene expression regulates pulsatile gonadotrophin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1–7 cell line. J. Neurosci. 23, 11 202–11 213.
| 1:CAS:528:DC%2BD3sXpvV2gtbc%3D&md5=f9b94ad21a37ca2d689624d87a1d7436CAS |
DeBruyne, J. P., Noton, E., Lambert, C. M., Maywood, E. S., Weaver, D. R., and Reppert, S. M. (2006). A clock shock: mouse CLOCK is not required for circadian oscillator function. Neuron 50, 465–477.
| A clock shock: mouse CLOCK is not required for circadian oscillator function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XkvFSgsbY%3D&md5=67772529c9ca5bdbdda005c3ce444970CAS | 16675400PubMed |
Dolatshad, H., Campbell, E. A., O’Hara, L., Maywood, E. S., Hastings, M. H., and Johnson, M. H. (2006). Developmental and reproductive performance in circadian mutant mice. Hum. Reprod. 21, 68–79.
| Developmental and reproductive performance in circadian mutant mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht1OqtL7J&md5=1be97c8182e23da7adef81bd890375ecCAS | 16210390PubMed |
Doring, B., Shynlova, O., Tsui, P., Eckardt, D., Janssen-Bienhold, U., Hofmann, F., Feil, S., Feil, R., Lye, S. J., and Willecke, K. (2006). Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition. J. Cell Sci. 119, 1715–1722.
| Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition.Crossref | GoogleScholarGoogle Scholar | 16595547PubMed |
Gallagher, P. J., and Herring, B. P. (1991). The carboxyl terminus of the smooth muscle myosin light chain kinase is expressed as an independent protein, telokin. J. Biol. Chem. 266, 23 945–23 952.
| 1:CAS:528:DyaK38Xlt1Gltrw%3D&md5=36034778447ece65b32ab7bdb9f7507fCAS |
Glattre, E., and Bjerkedal, T. (1983). The 24-hour rhythmicity of birth. A populational study. Acta Obstet. Gynecol. Scand. 62, 31–36.
| The 24-hour rhythmicity of birth. A populational study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3s3islSgug%3D%3D&md5=80a3bdf5261e0da0ac847515f562c149CAS | 6858620PubMed |
Herring, B. P., and Smith, A. F. (1996). Telokin expression is mediated by a smooth muscle cell-specific promoter. Am. J. Physiol. 270, C1656–C1665.
| 1:CAS:528:DyaK28Xktlagtb8%3D&md5=4dd67f613ed404432a365037b1283880CAS | 8764148PubMed |
Herzog, E. D., Grace, M. S., Harrer, C., Williamson, J., Shinohara, K., and Block, G. D. (2000). The role of Clock in the developmental expression of neuropeptides in the suprachiasmatic nucleus. J. Comp. Neurol. 424, 86–98.
| The role of Clock in the developmental expression of neuropeptides in the suprachiasmatic nucleus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXlvVemt7g%3D&md5=6451faf086026e7b28eb23ba60c5710cCAS | 10888741PubMed |
Kaiser, I. H., and Halberg, F. (1962). Circadian periodic aspects of birth. Ann. N. Y. Acad. Sci. 98, 1056–1068.
| Circadian periodic aspects of birth.Crossref | GoogleScholarGoogle Scholar | 13961851PubMed |
Kennaway, D. J., Boden, M. J., and Voultsios, A. (2004). Reproductive performance in female Clock Delta19 mutant mice. Reprod. Fertil. Dev. 16, 801–810.
| Reproductive performance in female Clock Delta19 mutant mice.Crossref | GoogleScholarGoogle Scholar | 15740704PubMed |
King, D. P., Vitaterna, M. H., Chang, A. M., Dove, W. F., Pinto, L. H., Turek, F. W., and Takahashi, J. S. (1997a). The mouse Clock mutation behaves as an antimorph and maps within the W19H deletion, distal of Kit. Genetics 146, 1049–1060.
| 1:CAS:528:DyaK2sXmsVartbY%3D&md5=066fa67b6230f0a3cf55052cd49251bdCAS | 9215907PubMed |
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., Turek, F. W., and Takahashi, J. S. (1997b). Positional cloning of the mouse circadian clock gene. Cell 89, 641–653.
| Positional cloning of the mouse circadian clock gene.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXjsVSnu74%3D&md5=034f826a3643b4b21960b77daa8c376eCAS | 9160755PubMed |
Knutsson, A. (2003). Health disorders of shift workers. Occup. Med. (Lond.) 53, 103–108.
| Health disorders of shift workers.Crossref | GoogleScholarGoogle Scholar |
Lee, E. C., Yu, D., Martinez de Velasco, J., Tessarollo, L., Swing, D. A., Court, D. L., Jenkins, N. A., and Copeland, N. G. (2001). A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics 73, 56–65.
| A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXisVykurg%3D&md5=acf5f1acdd16f5b5b1aea63910ce4194CAS | 11352566PubMed |
Lincoln, D. W., and Porter, D. G. (1976). Timing of the photoperiod and the hour of birth in rats. Nature 260, 780–781.
| Timing of the photoperiod and the hour of birth in rats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE287nsVGitA%3D%3D&md5=9d776307cdf3e24a6cd071af0477477bCAS | 1264254PubMed |
Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method. Methods 25, 402–408.
| Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=c02316d2aa02af4c464251269a77c9c9CAS | 11846609PubMed |
McDearmon, E. L., Patel, K. N., Ko, C. H., Walisser, J. A., Schook, A. C., Chong, J. L., Wilsbacher, L. D., Song, E. J., Hong, H. K., Bradfield, C. A., and Takahashi, J. S. (2006). Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science 314, 1304–1308.
| Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1agt7jF&md5=5fadea8313703261b19aace7822e2821CAS | 17124323PubMed |
Miller, B. H., Olson, S. L., Turek, F. W., Levine, J. E., Horton, T. H., and Takahashi, J. S. (2004). Circadian clock mutation disrupts oestrous cyclicity and maintenance of pregnancy. Curr. Biol. 14, 1367–1373.
| Circadian clock mutation disrupts oestrous cyclicity and maintenance of pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmsVKmsrw%3D&md5=d23c5a3a48829033136dd7a563ba2cc7CAS | 15296754PubMed |
Murray, S. A., Morgan, J. L., Kane, C., Sharma, Y., Heffner, C. S., Lake, J., and Donahue, L. R. (2010). Mouse gestation length is genetically determined. PLoS ONE 5, e12418.
| Mouse gestation length is genetically determined.Crossref | GoogleScholarGoogle Scholar | 20811634PubMed |
Ratajczak, C. K., and Muglia, L. J. (2008). Insights into parturition biology from genetically altered mice. Pediatr. Res. 64, 581–589.
| Insights into parturition biology from genetically altered mice.Crossref | GoogleScholarGoogle Scholar | 18679156PubMed |
Ratajczak, C. K., Boehle, K. L., and Muglia, L. J. (2009). Impaired steroidogenesis and implantation failure in Bmal1–/– mice. Endocrinology 150, 1879–1885.
| Impaired steroidogenesis and implantation failure in Bmal1–/– mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXktVWlsL0%3D&md5=ce633336bea59f7486c533ecd9808229CAS | 19056819PubMed |
Ratajczak, C. K., Herzog, E. D., and Muglia, L. J. (2010). Clock gene expression in gravid uterus and extra-embryonic tissues during late gestation in the mouse. Reprod. Fertil. Dev. 22, 743–750.
| Clock gene expression in gravid uterus and extra-embryonic tissues during late gestation in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlsVCqtLg%3D&md5=d18b70db929b740fd4f9034f30d896cdCAS | 20450826PubMed |
Reppert, S. M., and Weaver, D. R. (2002). Coordination of circadian timing in mammals. Nature 418, 935–941.
| Coordination of circadian timing in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XmsFWksb0%3D&md5=63dbcf27fafef4aade7e1a76c490a98dCAS | 12198538PubMed |
Reppert, S. M., Henshaw, D., Schwartz, W. J., and Weaver, D. R. (1987). The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain. Brain Res. 403, 398–402.
| The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s7lvVOrtA%3D%3D&md5=ac59654e5338457dcd1e3d37360fac7aCAS | 3828831PubMed |
Roizen, J., Luedke, C. E., Herzog, E. D., and Muglia, L. J. (2007). Oxytocin in the circadian timing of birth. PLoS ONE 2, e922.
| Oxytocin in the circadian timing of birth.Crossref | GoogleScholarGoogle Scholar | 17895964PubMed |
Storch, K. F., Paz, C., Signorovitch, J., Raviola, E., Pawlyk, B., Li, T., and Weitz, C. J. (2007). Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information. Cell 130, 730–741.
| Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVels7%2FF&md5=f089d58bf6a807c07d9f4bbd4ab26a64CAS | 17719549PubMed |
Vitaterna, M. H., King, D. P., Chang, A. M., Kornhauser, J. M., Lowrey, P. L., McDonald, J. D., Dove, W. F., Pinto, L. H., Turek, F. W., and Takahashi, J. S. (1994). Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behaviour. Science 264, 719–725.
| Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behaviour.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXktVagsLs%3D&md5=02c9a531c546c0896394591431d4f71fCAS | 8171325PubMed |
