Targeted Disruption of the <i>mPer3</i> Gene: Subtle Effects on Circadian Clock Function

Shearman, Lauren P.; Jin, Xiaowei; Lee, Choogon; Reppert, Steven M.; Weaver, David R.

doi:10.1128/mcb.20.17.6269-6275.2000

Cited by 274 publications

(187 citation statements)

References 38 publications

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“…All these polymorphisms are located in genes believed to encode for transcription regulatory factors. Mutations in CLOCK and the Period genes cause circadian rhythm disturbances in mice (King et al, 1997;Zheng et al, 2001;Shearman et al, 2000), although disruption of the Period3 gene has only a subtle effect (Shearman et al, 2000). NPAS2, or neuronal PAS domain protein 2, is a functional analogue of CLOCK, but unlike the other three genes it is not expressed in the hypothalamic suprachiasmatic nucleus, where the master pacemaker of the mammalian circadian system resides (Shearman et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Johansson

Willeit

Smedh

et al. 2002

Neuropsychopharmacol

304

189

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Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness-eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n ¼ 177) and diurnal preference (n ¼ 92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (w 2 ¼ 9.90, Bonferroni corrected P ¼ 0.035), indicating a recessive effect of the leucine allele on disease susceptibility (w 2 ¼ 6.61, Bonferroni corrected P ¼ 0.050). Period3 647 Val/Gly was associated with self-reported morningness-eveningness scores (n ¼ 92, oneway ANOVA: F ¼ 4.99, Bonferroni corrected P ¼ 0.044), with higher scores found in individuals with at least one glycine allele (t ¼ 3.1, Bonferroni corrected P ¼ 0.013). A second, population-based sample of individuals selected for high (n ¼ 127) or low (n ¼ 98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case-control material (n ¼ 177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

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Section: Introductionmentioning

confidence: 99%

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Johansson

Willeit

Smedh

et al. 2002

Neuropsychopharmacol

304

189

View full text Add to dashboard Cite

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“…Three per genes have been identified in the mouse that play distinct roles in the circadian clock mechanism (6,13). Whereas mper1 and mper2 seem to be essential, mper3 is dispensable for circadian rhythmicity (14). Both mper1 and mper2 are expressed with a circadian rhythm and are rapidly induced in the suprachiasmatic nucleus by light pulses delivered during the subjective night but not during the subjective day (6,15,16).…”

mentioning

confidence: 99%

E-box function in a period gene repressed by light

Vallone

Gondi

Whitmore

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

140

180

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In most organisms, light plays a key role in the synchronization of the circadian timing system with the environmental day-night cycle. Light pulses that phase-shift the circadian clock also induce the expression of period (per) genes in vertebrates. Here, we report the cloning of a zebrafish per gene, zfper4, which is remarkable in being repressed by light. We have developed an in vivo luciferase reporter assay for this gene in cells that contain a light-entrainable clock. High-definition bioluminescence traces have enabled us to accurately measure phase-shifting of the clock by light. We have also exploited this model to study how four E-box elements in the zfper4 promoter regulate expression. Mutagenesis reveals that the integrity of these four E-boxes is crucial for maintaining low basal expression together with robust rhythmicity and repression by light. Importantly, in the context of a minimal heterologous promoter, the E-box elements also direct a robust circadian rhythm of expression that is significantly phase-advanced compared with the original zfper4 promoter and lacks the light-repression property. Thus, these results reveal flexibility in the phase and light responsiveness of E-box-directed rhythmic expression, depending on the promoter context.

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“…Em 2000, foi gerado o primeiro animal knockout PER3 (KO Per3) (Shearman et al, 2000b) Em resumo, os primeiros trabalhos publicados (Zylka et al, 1998;Takumi et al, 1998) não mostraram nenhuma diferença na fase de expressão do gene PER3 às respostas agudas a pulsos de luz. Porém, com o passar dos anos, novas hipóteses foram sugeridas para o papel do gene PER3 (Pereira et al, 2005;Viola et al, 2007), especificamente com seu envolvimento na resposta à luz.…”

Section: O Gene Per3 E Sua Participação No Relógio Biológicounclassified

Period3: um gene relacionado com a sincronização de ritmos circadianos pela luz

Pereira¹,

Sabino²,

Umemura³

2012

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Resumo. O gene Period 3 (Per3) faz parte do mecanismo de temporização dos mamíferos. Os trabalhos publicados na literatura até hoje mostram alguns resultados conflitantes em relação à função deste gene, que ainda não está totalmente esclarecida. Em humanos, o gene Per3 possui um polimorfismo de repetição provavelmente associado com mecanismos homeostáticos e circadianos do sono. Alguns estudos especulam sobre o papel deste gene e de seu polimorfismo em relação a sensibilidade à luz e já foram publicados resultados bem interessantes. Estes estudos podem trazer grandes impactos terapêuticos, ajudando no tratamento de distúrbios dos ritmos biológicos, na redução de sintomas relacionados a jet lag e a trabalhos em turno. Palavras-chave. Genes do relógio; Gene Period3 (Per3); Sincronização à luz.Abstract. Period3 (Per3) is a clock gene that participates in the temporal mechanism in mammals. Papers have been published showing some conflicting results related with the function of this gene, which has not been completely established. In humans, Per3 gene contains a length polymorphism which is associated with homeostatic and circadian parameters of sleep. Some studies speculate on the function of this gene and its polymorphism in the sensitivity of light and recently, rather interesting data have been presented in the literature. These studies can help to improve the treatment of rhythms disorders and help to attenuate symptoms related with jet lag and shift work. Keywords. Clock genes; Period3 (Per3); Light synchronization. Contato do autor: danyellap@gmail.com IntroduçãoO sistema circadiano tem um papel na escolha do horário do sono e da vigília. Alguns ritmos são considerados marcadores circadianos, como, por exemplo, o ritmo da melatonina (também chamada "hormônio do escuro", pois tem como função sinalizar para o organismo a presença dessa fase) e o ritmo da temperatura central (que varia diariamente, atingindo valores mínimos entre a metade e o final da noite) (Derk-Jan e Simon, 2010).Uma série de pesquisas realizadas em animais e humanos tem demonstrado que polimorfismos nos genes relógio podem estar envolvidos com a suscetibilidade a distúrbios de ritmo e, em humanos, podem regular fenó-tipos circadianos, como a matutinidade e a vespertinidade (Archer et al, 2003;Carpen et al, 2006; Ebisawa et al, 2001;Katzenberg et al, 1998;Pedrazzoli et al, 2007;Pereira et al, 2005;Robilliard et al, 2002).Dentre os inúmeros genes reguladores do relógio biológico, o gene PER3 possui um polimorfismo de repetição específico de primatas que constitui um VNTR (número variável de repetições em sequência, em tradução livre). O número de repetições dos 54 pares de bases nitrogenadas constituintes deste polimorfismo é específico para cada espécie de primatas. Em humanos, esta repetição pode variar entre quatro e cinco vezes, levando aos pesquisadores a buscarem respostas sobre como as variáveis deste polimorfismo podem estar associadas com a ritmicidade circadiana.Estudos publicados na literatura especializada mostram associações deste ...

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Targeted Disruption of the mPer3 Gene: Subtle Effects on Circadian Clock Function

Cited by 274 publications

References 38 publications

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

E-box function in a period gene repressed by light

Period3: um gene relacionado com a sincronização de ritmos circadianos pela luz

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