Circadian abnormalities in mouse models of smith–magenis syndrome: Evidence for involvement of RAI1
Open accessAbstract
Smith–Magenis syndrome (SMS; OMIM 182290) is a genomic disorder characterized by multiple congenital anomalies, intellectual disability, behavioral abnormalities, and disordered sleep resulting from an ∼3.7 Mb deletion copy number variant (CNV) on chromosome 17p11.2 or from point mutations in the gene RAI1. The reciprocal duplication of this region results in another genomic disorder, Potocki–Lupski syndrome (PTLS; OMIM 610883), characterized by autism, intellectual disability, and congenital anomalies. We previously used chromosome‐engineering and gene targeting to generate mouse models for PTLS (Dp(11)17/+), and SMS due to either deletion CNV or gene knock‐out (Df(11)17‐2/+ and Rai1+/−, respectively) and we observed phenotypes in these mouse models consistent with their associated human syndromes. To investigate the contribution of individual genes to the circadian phenotypes observed in SMS, we now report the analysis of free‐running period lengths in Rai1+/− and Df(11)17‐2/+ mice, as well as in mice deficient for another known circadian gene mapping within the commonly deleted/duplicated region, Dexras1, and we compare these results to those previously observed in Dp(11)17/+ mice. Reduced free‐running period lengths were seen in Df(11)17‐2/+, Rai1+/−, and Dexras1−/−, but not Dexras1+/− mice, suggesting that Rai1 may be the primary gene underlying the circadian defects in SMS. However, we cannot rule out the possibility that cis effects between multiple haploinsufficient genes in the SMS critical interval (e.g., RAI1 and DEXRAS1) either exacerbate the circadian phenotypes observed in SMS patients with deletions or increase their penetrance in certain environments. This study also confirms a previous report of abnormal circadian function in Dexras1−/− mice. © 2013 Wiley Periodicals, Inc.
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Mice with a heterozygous deletion of Rai1 display a shortened locomotor activity period, although these mice are of mixed genetic background containing C57BL/6, which do not produce pineal melatonin.
“Mice with a heterozygous deletion of Rai1 display a shortened locomotor activity period133,134, although these mice are of mixed genetic background containing C57BL/6, which do not produce pineal melatonin.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [134]
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Cites
Potocki, L., Bi, W., Treadwell‐Deering, D., Carvalho, C. M. B., Eifert, A., Friedman, E. M., Glaze, D. G., Krull, K. R., Lee, J. A., Lewis, R. A., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/512864 · Cited by 425 · see citing works
Self-citationAutosomal XX sex reversal caused by duplication ofSOX9
Huang, B., Wang, S., Ning, Y., Lamb, A. N., & Bartley, J. A. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19991203)87:4 · Cited by 424 · see citing works
Potocki, L., Chen, K.-S., Park, S. S., Osterholm, D. E., Withers, M. A., Kimonis, V. E., Summers, A. M., Meschino, W. S., Anyane‐Yeboa, K., Kashork, C. D., et al. (2000) · Nature Genetics · doi:10.1038/71743 · Cited by 420 · see citing works
Self-citationClan Genomics and the Complex Architecture of Human Disease
Lupski, J. R., Belmont, J. W., Boerwinkle, E., & Gibbs, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.008 · Cited by 366 · see citing works
Self-citationMutations in RAI1 associated with Smith-Magenis syndrome
Slager, R. E., Newton, T. L., Vlangos, C. N., Finucane, B., & Elsea, S. H. (2003) · Nature Genetics · doi:10.1038/ng1126 · Cited by 362 · see citing works
Greenberg, F., Guzzetta, de Oca-Luna, R. M., Magenis, R. E., Smith, A. C., Richter, S. F., Kondo, I., Dobyns, W. B., Patel, P. I., & Lupski (1991) · PubMed · Cited by 340 · see citing works
Wei, N., Tsuge, T., Serino, G., Dohmae, N., Takio, K., Matsui, M., & Deng, X. (1998) · Current Biology · doi:10.1016/s0960-9822(07)00372-7 · Cited by 247 · see citing works
Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome
Potocki, L., Glaze, D., Tan, D.-X., Park, S.-S., Kashork, C. D., Shaffer, L. G., Reiter, R. J., & Lupski, J. R. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.6.428 · Cited by 244 · see citing works
Self-citationInversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome
Leersnyder, H. D., de Blois, M., Claustrat, B., Romana, S. P., Albrecht, U., von Kleist-Retzow, J., Delobel, B., Viot, G., Lyonnet, S., Vekemans, M. J. J., et al. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.115018 · Cited by 198 · see citing works
Appearances can be deceiving: phenotypes of knockout mice
Barbaric, I., Miller, G., & Dear, T. N. (2007) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elm008 · Cited by 195 · see citing works
Gender, genotype, and phenotype differences in Smith–Magenis syndrome: a meta‐analysis of 105 cases
Edelman, E., Girirajan, S., Finucane, B. M., Patel, P. I., Lupski, J., Smith, A., & Elsea, S. H. (2007) · Clinical Genetics · doi:10.1111/j.1399-0004.2007.00815.x · Cited by 166 · see citing works
Self-citationNeurologic and Developmental Features of the Smith-Magenis Syndrome (del 17p11.2)
Gropman, A. L., Duncan, W. C., & Smith, A. C. M. (2006) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.08.018 · Cited by 155 · see citing works
Iwahana, E., Karatsoreos, I., Shibata, S., & Silver, R. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.11.014 · Cited by 127 · see citing works
RAI1 variations in Smith–Magenis syndrome patients without 17p11.2 deletions
Girirajan, S., Elsas, L. J., Devriendt, K., & Elsea, S. H. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2005.031211 · Cited by 122 · see citing works
Williams, S. R., Zies, D., Mullegama, S. V., Grotewiel, M. S., & Elsea, S. H. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.04.013 · Cited by 115 · see citing works
Dexras1 Potentiates Photic and Suppresses Nonphotic Responses of the Circadian Clock
Cheng, H. M., Obrietan, K. H., Cain, S. W., Lee, B. Y., Agostino, P. V., Joza, N. A., Harrington, M. E., Ralph, M. R., & Penninger, J. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.021 · Cited by 113 · see citing works
Burns, B., Schmidt, K., Williams, S. R., Kim, S., Girirajan, S., & Elsea, S. H. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq317 · Cited by 113 · see citing works
De Leersnyder, H., de Blois, M.-C., Vekemans, M., Sidi, D., Villain, E., Kindermans, C., & Munnich, A. (2001) · Journal of Medical Genetics · doi:10.1136/jmg.38.9.586 · Cited by 113 · see citing works
Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome
Bi, W., Saifi, G. M., Shaw, C. J., Walz, K., Fonseca, P., Wilson, M., Potocki, L., & Lupski, J. R. (2004) · Human Genetics · doi:10.1007/s00439-004-1187-6 · Cited by 110 · see citing works
Self-citationRetinoic Acid Signaling Affects Cortical Synchrony During Sleep
Maret, S., Franken, P., Dauvilliers, Y. A., Ghyselinck, N. B., Chambon, P., & Tafti, M. (2005) · Science · doi:10.1126/science.1117623 · Cited by 107 · see citing works
Bi, W., Ohyama, T., Nakamura, H., Yan, J., Visvanathan, J., Justice, M. J., & Lupski, J. R. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi085 · Cited by 97 · see citing works
Self-citationBoudreau, E. A., Johnson, K. P., Jackman, A. R., Blancato, J., Huizing, M., Bendavid, C., Jones, M., Chandrasekharappa, S. C., Lewy, A. J., Smith, A. C. M., et al. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32846 · Cited by 92 · see citing works
Bi, W., Yan, J., Shi, X., Yuva‐Paylor, L. A., Antalffy, B. A., Goldman, A. M., Yoo, J. W., Noebels, J. L., Armstrong, D. L., Paylor, R. E., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm128 · Cited by 83 · see citing works
Self-citationRai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2)
Walz, K., Paylor, R. E., Yan, J., Bi, W., & Lupski, J. R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28953 · Cited by 78 · see citing works
Self-citationBehavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2)
Walz, K. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddh044 · Cited by 74 · see citing works
Takahashi, H., Umeda, N., Tsutsumi, Y., Fukumura, R., Ohkaze, H., Sujino, M., van der Horst, G. T. J., Yasui, A., Inouye, S. T., Fujimori, A., et al. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00543-0 · Cited by 73 · see citing works
The Molecular Gatekeeper Dexras1 Sculpts the Photic Responsiveness of the Mammalian Circadian Clock
Cheng, H. M., Dziema, H., Papp, J., Mathur, D. P., Koletar, M. M., Ralph, M. R., Penninger, J. M., & Obrietan, K. H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4253-06.2006 · Cited by 64 · see citing works
Enriched rearing improves behavioral responses of an animal model for CNV-based autistic-like traits
Lacaria, M., Spencer, C. M., Gu, W., Paylor, R. E., & Lupski, J. R. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds124 · Cited by 59 · see citing works
Self-citationRAI1 point mutations, CAG repeat variation, and SNP analysis in non‐deletion Smith–Magenis syndrome
Bi, W., Saifi, G. M., Girirajan, S., Shi, X., Szomju, B. B., Firth, H. V., Magenis, R. E., Potocki, L., Elsea, S. H., & Lupski, J. R. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31510 · Cited by 50 · see citing works
Self-citationBoone, P. M., Reiter, R. J., Glaze, D. G., Tan, D., Lupski, J. R., & Potocki, L. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.34098 · Cited by 47 · see citing works
Self-citationCarpizo, R., Martínez, Á., Mediavilla, D., González, M., Abad, A., & Sánchez‐Barceló, E. J. (2006) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2006.04.055 · Cited by 44 · see citing works
Lacaria, M., Saha, P., Potocki, L., Bi, W., Yan, J., Girirajan, S., Burns, B., Elsea, S. H., Walz, K., Chan, L., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002713 · Cited by 42 · see citing works
Self-citationYan, J., Bi, W., & Lupski, J. R. (2007) · The American Journal of Human Genetics · doi:10.1086/512043 · Cited by 42 · see citing works
Self-citationChamovitz, D., & Glickman, M. H. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00775-3 · Cited by 38 · see citing works
Potocki, L., Chen, K., & Lupski, J. R. (1999) · Genomics · doi:10.1006/geno.1998.5748 · Cited by 31 · see citing works
Self-citationZubenko, G. S., Stiffler, J. S., Hughes, H. B., Hurtt, M. R., & Kaplan, B. B. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980328)81:2 · Cited by 18 · see citing works
Non-photic phase resetting of Dexras1 deficient mice: A more complicated story
Dallmann, R., & Mrosovsky, N. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.03.006 · Cited by 12 · see citing works
Further delineation of the acro-renal-ocular syndrome
(1996) · Pure Amsterdam UMC · doi:10.1002/(sici)1096-8628(19960329)62:3 · Cited by 1 · see citing works
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- Authors
- Lacaria, M., Gu, W., & Lupski, J. R.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Lupski, James R
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2013-05-23
- Volume
- 161
- Issue
- 7
- Pages
- 1561-1568
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- PMC
- PMC4086898
- OpenAlex
- W1967408505
- Cited by
- 28
- References
- 38
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part A (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institute of Neurological Disorders and Stroke (R01NS058529)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Smith-Magenis syndrome, Potocki-Lupski syndrome, RAI1, circadian rhythm, free-running period, Dexras1, chromosome 17p11.2, copy number variation, haploinsufficiency, mouse model, intellectual disability, sleep disorders
- MeSH terms
- Animals, Disease Models, Animal, Female, Humans, Running, Trans-Activators, Mice, Knockout, ras Proteins, Chronobiology Disorders, Mice, Smith-Magenis Syndrome
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