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Mice lacking Period 1 and Period 2 circadian clock genes exhibit blue cone photoreceptor defects
Author(s) -
AitHmyed Ouafa,
FelderSchmittbuhl MariePaule,
GarciaGarrido Marina,
Beck Susanne,
Seide Christina,
Sothilingam Vithiyanjali,
Tanimoto Naoyuki,
Seeliger Mathias,
Bennis Mohammed,
Hicks David
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12103
Subject(s) - per1 , biology , per2 , opsin , clock , circadian clock , circadian rhythm , microbiology and biotechnology , retina , retinal , endocrinology , neuroscience , rhodopsin , biochemistry
Many aspects of retinal physiology are modulated by circadian clocks, but it is unclear whether clock malfunction impinges directly on photoreceptor survival, differentiation or function. Eyes from wild‐type (WT) and Period1 ( Per1 ) and Period2 ( Per2 ) mutant mice ( Per1 Brdm1 Per2 Brdm1 ) were examined for structural (histology, in vivo imaging), phenotypical (RNA expression, immunohistochemistry) and functional characteristics. Transcriptional levels of selected cone genes [ red/green opsin ( Opn1mw ), blue cone opsin ( Opn1sw ) and cone arrestin ( Arr3 )] and one circadian clock gene ( RORb ) were quantified by real‐time polymerase chain reaction. Although there were no changes in general retinal histology or visual responses (electroretinograms) between WT and Per1 Brdm1 Per2 Brdm1 mice, compared with age‐matched controls, Per1 Brdm1 Per2 Brdm1 mice showed scattered retinal deformations by fundus inspection. Also, mRNA expression levels and immunostaining of blue cone opsin were significantly reduced in mutant mice. Especially, there was an alteration in the dorsal–ventral patterning of blue cones. Decreased blue cone opsin immunoreactivity was present by early postnatal stages, and remained throughout maturation. General photoreceptor differentiation was retarded in young mutant mice. In conclusion, deletion of both Per1 and Per2 clock genes leads to multiple discrete changes in retina, notably patchy tissue disorganization, reductions in cone opsin mRNA and protein levels, and altered distribution. These data represent the first direct link between Per1 and Per2 clock genes, and cone photoreceptor differentiation and function.