Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent.

Full Abstract

The circadian rhythmicity of hormone secretion, body temperature, and sleep/wakefulness results from an endogenous rhythm of neural activity generated by clock genes in the suprachiasmatic nucleus (SCN). One of these genes, Clock, has been considered essential for the generation of cellular rhythmicity centrally and in the periphery; however, melatonin-proficient Clock(Delta19) + MEL mutant mice retain melatonin rhythmicity, suggesting that their central rhythmicity is intact. Here we show that melatonin production in these mutants was rhythmic in constant darkness and could be entrained by brief single daily light pulses. Under normal light-dark conditions, per2 and prokineticin2 (PK2) mRNA expression was rhythmic in the SCN of Clock(Delta19) + MEL mice. Expression of Bmal1 and npas2 was not altered, whereas per1 expression was arrhythmic. In contrast to the SCN, per1 and per2 expression, as well as Bmal1 expression in liver and skeletal muscle, together with plasma corticosterone, was arrhythmic in Clock(Delta19) + MEL mutant mice in normal light-dark conditions. npas2 mRNA was also arrhythmic in liver but rhythmic in muscle. The Clock(Delta19) mutation does not abolish central rhythmicity and light entrainment, suggesting that a functional Clock homolog, possibly npas2, exists in the SCN. Nevertheless, the SCN of Clock(Delta19) + MEL mutant mice cannot maintain liver and muscle rhythmicity through rhythmic outputs, including melatonin secretion, in the absence of functional Clock expression in the tissues. Therefore, liver and muscle, but not SCN, have an absolute requirement for CLOCK, with as yet unknown Clock-independent factors able to generate the latter.

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Author information

Author/s: Kennaway, David J (DJ); Owens, Julie A (JA); Voultsios, Athena (A); Varcoe, Tamara J (TJ);

Affiliation: Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, Medical School, University of Adelaide, Frome Rd., Adelaide, South Australia 5000, Australia. david.kennaway(-atsign-)adelaide.edu.au

Journal and publication information

Publication Type: Journal Article

Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol), published in United States. (Language: eng)

Reference: 2006-Oct; vol 291 (issue 4) : pp R1172-80

Dates: Created 2006/09/12; Completed 2006/10/30; Revised 2007/11/19;

PMID: 16709646, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Basic Helix-Loop-Helix Transcription Factors - genetics
Cell Cycle Proteins
Circadian Rhythm - physiology
Corticosterone - blood
Darkness
Female
Gastrointestinal Hormones - genetics
Liver - physiology
Male
Melatonin - blood
Mice
Mice, Inbred BALB C

Mice, Inbred BALB C
Mice, Inbred CBA
Mice, Mutant Strains
Muscle, Skeletal - physiology
Nerve Tissue Proteins - genetics
Neuropeptides - genetics
Nuclear Proteins - genetics
Photoperiod
Pineal Gland - physiology
RNA, Messenger - analysis
Suprachiasmatic Nucleus - physiology
Trans-Activators - genetics
Transcription Factors - genetics

Associated Chemicals: BMAL1 protein (0) ; Basic Helix-Loop-Helix Transcription Factors (0) ; Cell Cycle Proteins (0) ; Clock protein (0) ; Gastrointestinal Hormones (0) ; Nerve Tissue Proteins (0) ; Neuropeptides (0) ; Npas2 protein, mouse (0) ; Nuclear Proteins (0) ; Per1 protein, mouse (0) ; Per2 protein, mouse (0) ; Prok2 protein, mouse (0) ; RNA, Messenger (0) ; Trans-Activators (0) ; Transcription Factors (0) ; Corticosterone (50-22-6) ; Melatonin (73-31-4)

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