Reduced light sensitivity of the circadian clock in a hypopigmented mouse mutant

Martha Hotz Vitaterna*, James C. Wu, Fred W. Turek, Lawrence H. Pinto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Pink-eyed dilution (p/p) is a recessive mutation in mice which results in reduced pigmentation of the retinal pigment epithelium, as well as alterations in visual pathways and function. We investigated whether this mutation also affects light information reaching the circadian clock. Entrainment to a 12 h light 12 h dark cycle and the free-running period in constant darkness were not affected by this mutation. Phase shifts in response to 1 h light pulses consisting of bright white light at either circadian time 16 or 24 also did not differ between mutant and wild-type C57BL/6J mice. However, when 5 min, 502 nm light pulses of 1.2 × 10-1 μW/cm2 or 4 × 10-2 μW/cm2 were given at circadian time 16, the mutant mice responded with significantly smaller phase shifts than the wild-type mice. When animals were transferred to constant light, the free-running period of wild-type mice was longer than that of mutant mice, a finding which is consistent with a sensitivity difference between mutant and wild-type mice. Horseradish peroxidase tracing of retinal innervation of the hypothalamic suprachiasmatic nuclei (SCN) - the location of a circadian pacemaker - revealed a reduced innervation of the SCN in mutant mice compared with wild-type mice. The total volume of the SCN, as determined by neutral red stain, was also reduced in mutant mice, although not to as great an extent as the retinal innervation. Taken together, these results indicate that while basic characteristics of circadian clock function are not altered by the pink-eyed dilution mutation, the sensitivity of the clock to light is reduced. Whether the reduced retinal innervation results in the decreased sensitivity of the clock to light, or whether the decreased sensitivity is a result of other unknown changes in the light input to the clock remains to be determined.

Original languageEnglish (US)
Pages (from-to)436-442
Number of pages7
JournalExperimental Brain Research
Volume95
Issue number3
DOIs
StatePublished - Aug 1993

Keywords

  • Activity rhythm
  • Mouse
  • Pink-eyed dilution
  • Retinal projection
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

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