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A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse
- Source :
- Journal of Neurochemistry. 143:100-111
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase (Aanat) transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 (Pax6) homeobox gene, known to regulate pineal development, was upregulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice. Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis. This article is protected by copyright. All rights reserved.
- Subjects :
- Male
0301 basic medicine
endocrine system
medicine.medical_specialty
Mice, 129 Strain
AANAT
Biology
Arylalkylamine N-Acetyltransferase
Pineal Gland
Biochemistry
Retina
Melatonin
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Pineal gland
0302 clinical medicine
Neuroendocrine Cells
Internal medicine
Conditional gene knockout
medicine
Animals
Visual Pathways
Eye Proteins
Homeodomain Proteins
Mice, Knockout
Suprachiasmatic nucleus
Gene Expression Profiling
Genes, Homeobox
Circadian Rhythm
030104 developmental biology
Endocrinology
medicine.anatomical_structure
nervous system
Forebrain
Female
Suprachiasmatic Nucleus
PAX6
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Retinohypothalamic tract
Transcription Factors
medicine.drug
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 143
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi.dedup.....38cb374021853f8517b87484f2d8ea64