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Publication : Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice.

First Author  Brzezinski JA 4th Year  2005
Journal  Invest Ophthalmol Vis Sci Volume  46
Issue  7 Pages  2540-51
PubMed ID  15980246 Mgi Jnum  J:99410
Mgi Id  MGI:3582114 Doi  10.1167/iovs.04-1123
Citation  Brzezinski JA 4th, et al. (2005) Loss of circadian photoentrainment and abnormal retinal electrophysiology in math5 mutant mice. Invest Ophthalmol Vis Sci 46(7):2540-51
abstractText  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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