Purchase this article with an account.
Hongwei Ma, Lynsie Morris, Jianhua Xu, Mark B. Frank, Melissa Bebak, Xi-Qin Ding; Gene Expression Alterations in Mouse Retina with Cone Cyclic Nucleotide-gated Channel Deficiency. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1621.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for color perception and visual acuity. Naturally occurring mutations in the channel subunits CNGA3 and CNGB3 are associated with achromatopsia, progressive cone dystrophy, and some forms of maculopathies, with mutations in CNGB3 alone accounting for over 50% of all known cases of achromatopsia. This work investigates the gene expression profiles in mouse retina with CNGB3 deficiency.
Because cones comprise only 3-5% of the total photoreceptor population in a wild-type mouse retina, we generated the mouse line with CNGB3 deficiency on a cone-dominant background, i.e., CNGB3-/-/Nrl-/- mice. Retinal RNAs were prepared from CNGB3-/-/Nrl-/- and Nrl-/- mice (at postnatal 30 days) and analyzed by Illumina microarrays. The microarray data were analyzed using a 5% FDR and functionally evaluated using Ingenuity IPA and iReporter software. QRT-PCR was performed to confirm the microarray findings.
We found that 330 genes were significantly altered, including 144 up- and 186 down-regulated genes, in the CNGB3-/-/Nrl-/- retina relative to Nrl-/- retina. Eighty of these differentially expressed genes having ≥1.5-fold change were grouped into 67 functional categories. These categories are associated with phototransduction, cGMP- and cAMP-mediated signaling, G-protein coupled receptor signaling, EIF2/EIF4 signaling and endoplasmic reticulum stress pathway, cell growth and transcriptional regulation, and cellular transportation. Twenty genes from these functional groups, including cone arrestin (Arr3), HMG-box transcription factor 1 (HBP1), basic leucine zipper transcription factor 2 (BACH2), dopamine receptor D4 (DRD4), histone deacetylase 5 (HDAC5), and kinesin family member 3A (KIF3A) were selected and validated by QRT-PCR.
CNGB3 deficiency differentially regulates expression of a wide range of retinal genes. Those that directly or indirectly affect cell processes such as phototransduction, cellular survival, transcription regulation, and transportation likely play a crucial role in the retinal adaptation to impaired cone phototransduction resulting from CNG channel deficiency.
This PDF is available to Subscribers Only