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RN Van Gelder, R Wee, L Gan; Lack of Photic Entrainment and Abnormal Free-Running Period in Math5-/Math5- Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1366.
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Purpose: Rods and cones are dispensable for photic signaling to the circadian clock in the suprachiasmatic nucleus (SCN). Mice lacking the math5 gene lack most retinal ganglion cells. We sought to determine the circadian phenotype of homozygous and heterozygous math5 knockout mice. Methods: Homozygous and heterozygous math5- mice were generated by appropriate crosses and confirmed by PCR genotyping. Wheel running activity was continuously monitored in bright light-dark conditions and in total darkness. Two-point photic phase response curves (PRC) were generated for heterozygote and wild-type mice. Entrainment to a non-photic stimulus (wheel locking) was also studied. Results: math5-/math5- mice showed no entrainment to bright light-dark cycles. The free-running tau of these mice was uniformly ∼1 hour longer than wild-type or heterozygous mice (math5-/math5- = 24.43 + 0.10 hr, n=7; math5+/math5- = 23.59 + 0.13 hr, n=7; math5+/math5+ = 23.62 hr, n=4). A two-point PRC showed no difference in phase shifting between wild-type and heterozygous mice. math5-/math5- mice showed abnormal entrainment to a non-photic stimulus. Conclusions: math5-dependent retinal ganglion cells are necessary for photic entrainment of circadian rhythms. Retinohypothalamic signaling partially determines the free-running period of the circadian oscillator. Mice lacking most retinal ganglion cells also demonstrate abnormal non-photic entrainment.
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