Aberrant Development of the Suprachiasmatic Nucleus and Circadian Rhythms in Mice Lacking the Homeodomain Protein Six6
| Autor: | Pamela L. Mellon, Daniel D. Clark, Michael R. Gorman, Jason D. Meadows, Megumi Hatori, Satchidananda Panda |
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| Rok vydání: | 2013 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Vasopressin Physiology Photoperiod Vasoactive intestinal peptide Biology Article Mice Physiology (medical) Internal medicine medicine Animals Circadian rhythm Skeleton Homeodomain Proteins Mice Knockout Suprachiasmatic nucleus beta-Galactosidase Circadian Rhythm Arginine Vasopressin Mice Inbred C57BL Endocrinology nervous system Light effects on circadian rhythm Hypothalamus Trans-Activators Optic nerve Homeobox Suprachiasmatic Nucleus sense organs hormones hormone substitutes and hormone antagonists Vasoactive Intestinal Peptide |
| Zdroj: | Journal of Biological Rhythms. 28:15-25 |
| ISSN: | 1552-4531 0748-7304 |
| DOI: | 10.1177/0748730412468084 |
| Popis: | The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus is the central pacemaker for peripheral and organismal circadian rhythms. The development of this hypothalamic structure depends on genetic programs throughout embryogenesis. We have investigated the role of the homeodomain transcription factor Six6 in the development of the SCN. We first showed that Six6 mRNA has circadian regulation in the mouse SCN. We then characterized the behavioral activity patterns of Six6-null mice under various photoperiod manipulations and stained their hypothalami using SCN-specific markers. Six6-null mice display abnormal patterns of circadian behavior indicative of SCN abnormalities. The ability of light exposure to reset rhythms correlates with the presence or absence of optic nerves, but all Six6-null mice show irregular rhythms. In contrast, wild-type mice with crushed optic nerves maintain regular rhythms regardless of light exposure. Using immunohistochemistry for arginine vasopressin (AVP), vasoactive intestinal polypeptide (VIP), and β-galactosidase, we demonstrated the lack of these SCN markers in all Six6-null mice regardless of the presence of optic nerve or partial circadian rhythms. Therefore, Six6 is required for the normal development of the SCN, and the Six6-null mouse can mount independent, although irregular, circadian rhythms despite the apparent absence of a histochemically defined SCN. |
| Databáze: | OpenAIRE |
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