Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized Müller glia cells

Rossum, Agnes G.S.H. van; Aartsen, Wendy M.; Meuleman, J.; Klooster, Jan; Malysheva, A.; Versteeg, Inge; Arsanto, Jean-Pierre; Bivic, André Le; Wijnholds, Jan

doi:10.1093/hmg/ddl194

Cited by 101 publications

(116 citation statements)

References 52 publications

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“…However, in contrast with the observation made in the Crb2Chx10 cKO (11,13), in the Crb2Crx cKO the lamination of ganglion, amacrine, bipolar and Müller glial cells was also affected, misplaced inner retinal cells were detected ectopically in the ONL. Similar defects in the lamination of these cells were also observed in CRB2 null retinas with half of the amount of CRB1 (Crb1 +/2 Crb2Chx10 cKO) (17).…”

Section: Discussioncontrasting

confidence: 95%

“…In the developing mouse retina, CRB2 was detected in retinal progenitor cells and in the adult retina in photoreceptors and Müller glial cells (11,13). In Crb2Crx cKO retinas, removal of CRB2 in photoreceptor precursor cells results in a severe phenotype, with an early onset (E15.5).…”

Section: Discussionmentioning

confidence: 99%

“…As a control, we used a CMV-GFP-H1-shMpp4 described before (13). MPP4 is present in the photoreceptor synapses and at lower levels at the subapical regions of photoreceptor cells (6).…”

Section: Human Molecularmentioning

confidence: 99%

“…In the developing and adult mouse retina, the apical Crumbs complex resides at the subapical region adjacent to the adherens junctions between the retinal progenitor cells (11) or between the photoreceptors and Müller glial cells (9,12). However, in the adult mouse retina, while CRB2 protein is present in both photoreceptor and Müller glial cells, CRB1 is detected only in Müller glial cells (13).…”

Section: Introductionmentioning

confidence: 99%

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Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

Alves¹,

Pellissier²,

Vos³

et al. 2014

Human Molecular Genetics

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In humans, the Crumbs homolog-1 (CRB1) gene is mutated in autosomal recessive Leber congenital amaurosis and early-onset retinitis pigmentosa. In mammals, the Crumbs family is composed of: CRB1, CRB2, CRB3A and CRB3B. Recently, we showed that removal of mouse Crb2 from retinal progenitor cells, and consequent removal from Mü ller glial and photoreceptor cells, results in severe and progressive retinal degeneration with concomitant loss of retinal function that mimics retinitis pigmentosa due to mutations in the CRB1 gene. Here, we studied the effects of cell-type-specific loss of CRB2 from the developing mouse retina using targeted conditional deletion of Crb2 in photoreceptors or Mü ller cells. We analyzed the consequences of targeted loss of CRB2 in the adult mouse retina using adeno-associated viral vectors encoding Cre recombinase and short hairpin RNA against Crb2. In vivo retinal imaging by means of optical coherence tomography on retinas lacking CRB2 in photoreceptors showed progressive thinning of the photoreceptor layer and cellular mislocalization. Electroretinogram recordings under scotopic conditions showed severe attenuation of the a-wave, confirming the degeneration of photoreceptors. Retinas lacking CRB2 in developing photoreceptors showed early onset of abnormal lamination, whereas retinas lacking CRB2 in developing Mü ller cells showed late onset retinal disorganization. Our data suggest that in the developing retina, CRB2 has redundant functions in Mü ller glial cells, while CRB2 has essential functions in photoreceptors. Our data suggest that short-term loss of CRB2 in adult mouse photoreceptors, but not in Mü ller glial cells, causes sporadic loss of adhesion between photoreceptors and Mü ller cells.

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Section: Discussioncontrasting

confidence: 95%

Section: Discussionmentioning

confidence: 99%

“…As a control, we used a CMV-GFP-H1-shMpp4 described before (13). MPP4 is present in the photoreceptor synapses and at lower levels at the subapical regions of photoreceptor cells (6).…”

Section: Human Molecularmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

Alves¹,

Pellissier²,

Vos³

et al. 2014

Human Molecular Genetics

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“…The great majority of inherited retinal degenerations are caused by gene defects affecting photoreceptor cells and relatively few are caused by defects affecting other cells types. [5][6][7][8][9][10] Development of gene supplementation therapy has therefore focussed primarily on gene transfer to photoreceptors.…”

Section: Inherited Retinal Degeneration As a Target For Gene Therapymentioning

confidence: 99%

Gene supplementation therapy for recessive forms of inherited retinal dystrophies

Smith¹,

Bainbridge²,

Ali³

2011

Gene Ther

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Over the last decade, gene supplementation therapy for inherited retinal degeneration has come of age. Early proof-of-concept studies in animal models of disease showed modest, but genuine improvements in retinal function and/or survival. Further development of the vectors used for gene transfer to the retina has led to better treatment efficacy in a wide variety of animal models, leading in 2008 to the initiation of three clinical trials for Leber congenital amaurosis caused by retinal pigment epithelium 65 deficiency. The results from these trials suggest that the treatment of inherited retinal dystrophy by gene therapy can be safe and effective. Here, we examine the progress of gene supplementation therapy in the retina, and discuss the potential for using gene therapy to treat different forms of inherited retinal degeneration.

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Current perspectives in Leber congenital amaurosis type 8 mouse modeling

Nahar

Cho

2022

Developmental Dynamics

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Mutations in the CRB1 (Crumbs homolog 1) cause rare retinal diseases like retinitis pigmentosa type 12 (RP12) and Leber congenital amaurosis type 8 (LCA8). RP12 results in progressively worsening peripheral vision, whereas LCA8 causes severe visual impairment at birth or in early life. While several mouse models have been proposed for RP12, few replicate the full spectrum of human LCA8 pathology, such as disorganized retinal layering, abnormal retinal thickening, pigmentary defects, hyperreflective lesions, and severely attenuated electroretinogram responses at birth. Six models have been proposed utilizing the Cre-loxP system to delete candidate genes in specific retinal cell types and developmental stages. The model ablating Crb1 and its homolog Crb2 (using mRx-Cre) from the beginning of the eye development is the most complete as it shows blindness during the eye-opening stage, pigmentary defects in the RPE, ganglion cell layer heterotopia, disruption of retinal lamination, and acellular patches. LCA8 represents a unique type of retinal dystrophy among LCA subtypes, driven by dysfunctional retinal progenitor cells during eye development. In contrast, other LCA types and RP12 are caused by photoreceptor defects. Therefore, the most accurate LCA8-like mouse model must target both alleles of the Crb1 and Crb2 genes in the optic vesicle or earlier.

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Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized Müller glia cells

Cited by 101 publications

References 52 publications

Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

Gene supplementation therapy for recessive forms of inherited retinal dystrophies

Current perspectives in Leber congenital amaurosis type 8 mouse modeling

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