Mapping Quantitative Trait Loci Affecting Circadian Photosensitivity in Retinally Degenerate Mice

Abstract

It is known that retinally degenerate C57BL/6J (rd/rd) mice have unattenuated circadian photosensitivity. However, the authors have previously found that CBA/J (rd/rd) mice that carry the same rd mutation have attenuated circadian photosensitivity compared to normal CBA/N (+/+) mice. In the present study, a quantitative trait locus (QTL) analysis using C57BL/6J (rd/rd) and CBA/J (rd/rd) mice was conducted in order to identify the genes affecting circadian photosensitivity of the rd mice. As a result, several putative QTLs on three separate chromosomes (8, 12, 17) were detected, which indicates that circadian photosensitivity in rd mice is altered by multiple genes. Identification of these genes may provide new insights into the understanding of regulation of circadian photoentrainment and sleep-wake disorders.

Keywords

quantitative trait loci circadian rhythm entrainment phase shift circadian photosensitivity rd mice immediate early gene

References

Akashi M and Nishida E (2000) Involvement of the MAP kinase cascade in resetting of the mammalian circadian clock. Genes Dev 14:645-649.

Aschoff J (1981) Freerunning and entrained circadian rhythms. In Handbook of Behavioral Neurobiology: Vol. 4. Biological Rhythms, J Aschoff , ed, pp 81-93, Plenum Press, New York.

Berson DM , Dunn FA , and Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070-1073.

Bowes C , Li T , Danciger M , Baxter LC , Applebury ML , and Farber DB (1990) Retinal degeneration in the rd mouse is caused by the [.beta] subunit of rod cGMP-phosphodiesterase. Nature 347:677-680.

Carter-Dawson LD , LaVail MM , and Sidman RL (1978) Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Visual Sci 17:489-498.

Churchill GA and Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138:963-971.

Doerge RW and Churchill GA (1996) Permutation tests for multiple loci affecting a quantitative character. Genetics 142:285-294.

Ebihara S and Tsuji K (1980) Entrainment of the circadian activity rhythm to the light cycle: Effective light intensity for a zeitgeber in the retinal degenerate C3H mouse and the normal C57BL mouse. Physiol Behav 24:523-527.

Foster RG , Provencio I , Hudson D , Fiske S , De Grip W , and Menaker M (1991) Circadian photoreception in the retinally degenerate mouse (rd/rd). J Comp Physiol A 169:39-50.

10.

Gooley JJ , Lu J , Chou TC , Scammell TE , and Saper CB (2001) Melanopsin in cells of origin of the retinohypothalamic tract. Nat Neurosci 4:1165-1165.

11.

Haley CS and Knott SA (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69:315-324.

12.

Hannibal J , Hindersson P , Knudsen SM , Georg B , and Fahrenkrug J (2002) The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide-containing retinal ganglion cells of the retinohypothalamic tract. J Neurosci 22(RC191):1-7.

13.

Hattar S , Liao HW , Takao M , Berson DM , and Yau KW (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295:1065-1070.

14.

Helfrich-Förster C , Winter C , Hofbauer A , Hall JC , and Stanewsky R (2001) The circadian clock of fruit flies is blind after elimination of all known photoreceptors. Neuron 30:249-261.

15.

Hofstetter JR and Mayeda AR (1998) Provisional quantitative trait loci (QTL) for the Aschoff effect in RI mice. Physiol Behav 64:97-101.

16.

Hofstetter JR , Mayeda AR , Possidente B , and Nurnberger JI Jr (1995) Quantitative trait loci (QTL) for circadian rhythms of locomotor activity in mice. Behav Genetics 25:545-556.

17.

Kornhauser JM , Nelson DE , Mayo KE , and Takahashi JS (1990) Photic and circadian regulation of c-fos gene expression in the hamster suprachiasmatic nucleus. Neuron 5:127-134.

18.

Kornhauser JM , Nelson DE , Mayo KE , and Takahashi JS (1992) Regulation of jun-B messenger RNA and AP-1 activity by light and a circadian clock. Science 255:1581-1584.

19.

Lander E and Botstein D (1989) Mapping mendelian factor underlying quantitative traits using RFLP linkage map. Genetics 121:185-199.

20.

Lucas RJ , Douglas RH , and Foster RG (2001) Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci 4:621-626.

21.

Obrietan K , Imprey S , and Storm DR (1998) Light and circadian rhythmicity regulate MAP kinase activation in the suprachiasmatic nuclei. Nat Neurosci 8:693-199.

22.

Pittendrigh CS (1981) Circadian systems: Entrainment. In Handbook of Behavioral Neurobiology: Vol. 4. Biological Rhythms, J Aschoff , ed, pp 95-124, Plenum Press, New York.

23.

Pittler SJ , Keeler SJ , Sidman RL , and Baehr W (1993) PCR analysis of DNA from 70-year-old sections of rodless retina demonstrates identity with the mouse rd defect. Proc Natl Acad Sci U S A 91:9616-9619.

24.

Pohl H (1976) Proportional effect of light on entrained circadian rhythms of birds and mammals. J Comp Physiol 112:103-108.

25.

Provencio I and Foster RG (1995) Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics. Brain Res 694:183-190.

26.

Provencio I , Rollag MD , and Castrucci AM (2002) Photoreceptive net in the mammalian retina. Nature 415:493-493.

27.

Rusak B , Robertson HA , Wisden W , and Hunt SP (1990) Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus. Science 248:1237-1240.

28.

Sanada K , Hayashi Y , Harada Y , Okano T , and Fukada Y (2000) Role of circadian activation of mitogen-activated protein kinase in chick pineal clock oscillation. J Neurosci 20:986-991.

29.

Schwartz WJ and Aronin N (1999) In the vanguard of SCN clock genes: Photoinducible c-fos was discovered ten years ago. Biol Rhythms Bull 1:2-5.

30.

Shimomura K , Low-Zeddies SS , King DP , Steeves TDL , Whiteley A , Kushla J , Zemenides PD , Lin A , Vitaterna MH , Churchill GA , and Takahashi JS (2001) Genome-wideepistatic interaction analysis reveals complex genetic determinants of circadian behavior in mice.Genome Res 11:959-980.

31.

Somers DE , Devlin PF , and Kay SA (1998) Phytochromes and cryptochromes in the entrainment of the Arabidopsis circadian clock. Science 282:1488-1490.

32.

Takahashi JS , DeCoursey PJ , Bauman L , and Menaker M (1984) Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature 308:186-188.

33.

Yoshimura T and Ebihara S (1996) Spectral sensitivity of photoreceptors mediating phase-shifts of circadian rhythms in retinally degenerate CBA/J (rd/rd) and normal CBA/N (+/+) mice. J Comp Physiol A 178:797-802.

34.

Yoshimura T and Ebihara S (1998) Decline of circadian photosensitivity associated with retinal degeneration in CBA/J-rd/rd mice. Brain Res 779:188-193.

35.

Yoshimura T , Nishio M , Goto M , and Ebihara S (1994) Differences in circadian photosensitivity between retinally degenerate CBA/J mice (rd/rd) and normal CBA/N (+/ +) mice. J Biol Rhythms 9:51-60.

36.

Yoshimura T , Suzuki Y , Makino E , Suzuki T , Kuroiwa A , Matsuda Y , Namikawa T , and Ebihara S (2000) Molecular analysis of avian circadian clock genes. Mol Brain Res 78:207-215.