myosin 7aa−/− mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses

Wasfy, Meagan M.; Matsui, Jonathan I.; Miller, J W; Dowling, John E.; Perkins, Brian D.

doi:10.1016/j.exer.2014.03.007

Cited by 37 publications

(35 citation statements)

References 60 publications

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“…; mutants presented with elevated cell death in the outer nuclear layer of the retina and photoreceptor degeneration. 83 A number of large acellular holes were observed in the RPE of myo7aa mutants following light damage by exposure to constant light conditions, consistent with an inability to clear outer segment debris and subsequent non-autonomous RPE degeneration.…”

Section: Retinitis Pigmentosamentioning

confidence: 97%

The zebrafish eye—a paradigm for investigating human ocular genetics

Richardson¹,

Tracey‐White²,

Webster

et al. 2016

Eye

153

162

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Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future.

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Section: Retinitis Pigmentosamentioning

confidence: 97%

The zebrafish eye—a paradigm for investigating human ocular genetics

Richardson¹,

Tracey‐White²,

Webster

et al. 2016

Eye

153

162

View full text Add to dashboard Cite

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“…In photoreceptors, delay of rhodopsin transport to the outer segment is shown in three different strains of Myo7a mutant mice and myo7aa ty229d/ty229d zebrafish (Zebrafish has two human MYO7A orthologs, myo7aa and myo7ab .) [150, 151]. The role of myosin VIIa in rhodopsin transport is proposed to be achieved through direct interaction of myosin VIIa with spectrin-βV, an adaptor protein associating with rhodopsin, kinesin-II and the dynein complex [152].…”

Section: Functional Studies Of Ush Gene Productsmentioning

confidence: 99%

“…Physiological and histological studies in various Myo7a mutant mouse and myo7aa mutant zebrafish retinas produced somewhat inconsistent results, possibly resulting from different mutant species and strains, genetic backgrounds, retinal pigmentation levels and light illumination levels used in the experiments [149, 151, 153–155]. Electroretinogram (ERG) recording is a non-invasive technique to measure retinal electrical responses to light stimuli with resulting a- and b-waves representing responses from photoreceptors and inner retinal neurons, respectively.…”

Section: Functional Studies Of Ush Gene Productsmentioning

confidence: 99%

“…Electroretinogram (ERG) recording is a non-invasive technique to measure retinal electrical responses to light stimuli with resulting a- and b-waves representing responses from photoreceptors and inner retinal neurons, respectively. Myo7a 4626SB/4626SB , Myo7a 816SB/816SB , Myo7a 7J/7J , Myo7a 8J/8J and Myo7a 9J/9J mice and myo7aa ty229d/ty229d mutant zebrafish exhibit reduced ERG a- and b-wave amplitudes but normal light sensitivity [151, 155], while albino Myo7a 4626SB/4626SB mice show an age-dependent reduction of ERG b-wave, less light sensitivity and slow recovery from light desensitization [154]. In myo7aa ty229d/ty229d zebrafish, mild retinal degeneration, indicated by photoreceptor loss, was observed at 10 days postfertilization [151], while no retinal degeneration occurs in all Myo7a mutant mice examined under normal husbandry conditions.…”

Section: Functional Studies Of Ush Gene Productsmentioning

confidence: 99%

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Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

Mathur

Yang

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

285

301

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Usher syndrome (USH), clinically and genetically heterogeneous, is the leading genetic cause of combined hearing and vision loss. USH is classified into three types, based on the hearing and vestibular symptoms observed in patients. Sixteen loci have been reported to be involved in the occurrence of USH and atypical USH. Among them, twelve have been identified as causative genes and one as a modifier gene. Studies on the proteins encoded by these USH genes suggest that USH proteins interact among one another and function in multiprotein complexes in vivo. Although their exact functions remain enigmatic in the retina, USH proteins are required for the development, maintenance and function of hair bundles, which are the primary mechanosensitive structure of inner ear hair cells. Despite the unavailability of a cure, progress has been made to develop effective treatments for this disease. In this review, we focus on the most recent discoveries in the field with an emphasis on USH genes, protein complexes and functions in various tissues as well as progress toward therapeutic development for USH.

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“…14,15 The protein MYO7A is an unconventional myosin expressed in multiple epithelial cell types, 16 including the RPE, where it functions in the light-dependent localization of the visual cycle enzyme, RPE65. 17 It is also expressed in the photoreceptor calyceal processes and cilia, and the stereocilia, together with other USH proteins.…”

mentioning

confidence: 99%

A Founder Mutation inMYO7AUnderlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora

Roberts

George

Greenberg

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Roberts L, George S, Greenberg J, Ramesar RS. A founder mutation in MYO7A underlies a significant proportion of Usher syndrome in indigenous South Africans: implications for the African diaspora. Invest Ophthalmol Vis Sci. 2015;56:6671-6678. DOI:10.1167/iovs.15-17028 PURPOSE. Research over the past 25 years at the University of Cape Town has led to the identification of causative mutations in 17% of the 1416 families in the Retinal Degenerative Diseases (RDD) biorepository in South Africa. A low rate of mutation detection has been observed in patients of indigenous African origin, hinting at novel genes and mutations in this population. Recently, however, data from our translational research program showed two unrelated indigenous African families with Usher syndrome (USH), with the same homozygous MYO7A mutation. Therefore, the extent to which this mutation contributes toward the disease burden in South Africa was investigated. METHODS. Cohorts of unrelated indigenous SouthAfrican probands with different RDD diagnoses were tested for the MYO7A c.6377delC mutation. Familial cosegregation analysis was performed for homozygous probands, clinical data were evaluated, and SNP haplotypes were analyzed.RESULTS. This homozygous MYO7A mutation underlies a remarkable 43% of indigenous African USH cases investigated in this study, the majority of which (60%) were diagnosed clinically with Type 2 USH. All homozygotes shared a common haplotype. This mutation does not appear to cause nonsyndromic vision loss. CONCLUSIONS.Of interest is the origin of this common mutation relevant to the Bantu population migration into southern Africa. Further investigation of the phenotype may elucidate the disease biology, and perhaps reveal a larger cohort with the same mutation, with which to assess the impact of environmental and genetic modifiers and evaluate therapeutic trials.

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myosin 7aa−/− mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses

Cited by 37 publications

References 60 publications

The zebrafish eye—a paradigm for investigating human ocular genetics

The zebrafish eye—a paradigm for investigating human ocular genetics

Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

A Founder Mutation inMYO7AUnderlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora

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