Loss of Circadian Photoentrainment and Abnormal Retinal Electrophysiology in Math5 Mutant Mice
Abstract
PURPOSE: To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and retinal function. METHODS: The wheel-running behavior of wild-type and Math5 mutant mice was measured under various light-dark cycle conditions. To evaluate retinal input to the suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were labeled in vivo. To assess changes in retinal function, corneal flash electroretinograms (ERGs) from mutant and wild-type mice were compared under dark- and light-adapted conditions. Alterations in retinal neuron populations were evaluated quantitatively and with cell-type-specific markers. RESULTS: The Math5-null mice did not entrain to light and exhibited free-running circadian behavior with a mean period (23.6 +/- 0.15 hours) that was indistinguishable from that of wild-type mice (23.4 +/- 0.19 hours). The SCN showed no anterograde labeling with a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs recorded from mutant mice had diminished scotopic a- and b-wave and photopic b-wave amplitudes. The scotopic b-wave was more severely affected than the a-wave. The oscillatory potentials (OPs) and scotopic threshold response (STR) were also reduced. Consistent with these ERG findings, a pan-specific reduction in the number of bipolar cells and a smaller relative decrease in the number of rods in mutant mice were observed. CONCLUSIONS: Math5-null mice are clock-blind and have no RGC projections to the SCN. RGCs are thus essential for photoentrainment in mice, but are not necessary for the development or intrinsic function of the SCN clock. RGCs are not required to generate any of the major ERG waveforms in mice, including the STR, which is produced by ganglion cells in some other species. The diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most likely caused by the decreased abundance of retinal interneurons.
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Mice with ATOH7 knocked out are unable to entrain their circadian clock based on light stimuli.
“ATOH7 is a circadian gene that is involved in retinal ganglion cell development, and mice with this gene knocked out are unable to entrain their circadian clock based on light stimuli (Brzezinski et al. 2005).”
From Archaic Introgression Shaped Human Circadian Traits (2023) · cites this paper as Brzezinski et al. 2005
ATOH7 is a circadian gene involved in retinal ganglion cell development.
“ATOH7 is a circadian gene that is involved in retinal ganglion cell development, and mice with this gene knocked out are unable to entrain their circadian clock based on light stimuli (Brzezinski et al. 2005).”
From Archaic Introgression Shaped Human Circadian Traits (2023) · cites this paper as Brzezinski et al. 2005
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- Authors
- Brzezinski, J. A., Brown, N. L., Tanikawa, A., Bush, R. A., Sieving, P. A., Vitaterna, M. H., Takahashi, J. S., & Glaser, T.
- Affiliations
- University of Michigan (US)
- University of Cincinnati (US)
- National Institutes of Health (US)
- Northwestern University (US)
- ORCID
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2005-07-01
- Volume
- 46
- Issue
- 7
- Pages
- 2540
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2020599095
- Cited by
- 60
- References
- 97
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Eye Institute (T32 EY13934, EY 13612, R01EY013612, EY11729, R01EY014259, R01EY011729, T32EY013934)
- National Institute of General Medical Sciences (T32GM007544, T32 GM07544)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- Math5, Atoh7, retinal ganglion cells, circadian photoentrainment, suprachiasmatic nucleus, retinohypothalamic tract, electroretinogram, scotopic b-wave, oscillatory potentials, scotopic threshold response, bipolar cells, rod photoreceptors, retinal interneurons, free-running period, retinal development
- MeSH terms
- Animals, Circadian Rhythm, Dark Adaptation, Electrophysiology, Electroretinography, Interneurons, Light, Mice, Inbred C57BL, Mice, Mutant Strains, Nerve Tissue Proteins, Retina, Retinal Degeneration, Retinal Ganglion Cells, Suprachiasmatic Nucleus, Transcription Factors, Visual Pathways, Photoperiod, Helix-Loop-Helix Motifs, Mice, Knockout, Microscopy, Confocal, Chronobiology Disorders, Mice, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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