ArticleInvestigative ophthalmology & visual science2014
Transgenic expression of constitutively active RAC1 disrupts mouse rod morphogenesis.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
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- RAC1 controls progressive movement and competitiveness of mammalian spermatozoa.PLoS genetics · 2021Article
- Effect of conditional deletion of cytoplasmic dynein heavy chain DYNC1H1 on postnatal photoreceptors.PloS one · 2021Article
- Trans-ocular Electric CurrentMolecular therapy. Methods & clinical development · 2019Article
- Conditional Dicer1 depletion using Chrnb4-Cre leads to cone cell death and impaired photopic vision.Scientific reports · 2019Article
- ADP-Ribosylation Factor-Like 2 (ARL2) regulates cilia stability and development of outer segments in rod photoreceptor neurons.Scientific reports · 2018Article
- A new functional role uncovered for RASGRF2 in control of nuclear migration in cone photoreceptors during postnatal retinal development.Small GTPases · 2017Article
- Photoreceptor oxidative stress in hyperoxia-induced proliferative retinopathy accelerates rd8 degeneration.PloS one · 2017Article
- The bacterial toxin CNF1 as a tool to induce retinal degeneration reminiscent of retinitis pigmentosa.Scientific reports · 2016Article
- microRNA regulatory circuits in a mouse model of inherited retinal degeneration.Scientific reports · 2016Article
- Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.Investigative ophthalmology & visual science · 2016Article
- ARL3 regulates trafficking of prenylated phototransduction proteins to the rod outer segment.Human molecular genetics · 2016Article
- NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice.Investigative ophthalmology & visual science · 2016Article
- HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome.Journal of medical genetics · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeDominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsin-null mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1.
methodsTransgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts.
resultsConstitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day (P)6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors.
conclusionsConstitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis.
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