Application of Fluorescent Proteins for Functional Dissection of the Drosophila Visual System

Smylla, Thomas K.; Wagner, Krystina; Huber, Armin

doi:10.3390/ijms22168930

Cited by 4 publications

(2 citation statements)

References 129 publications

(140 reference statements)

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“…The Drosophila eye has been used extensively to assess neural toxicity in a variety of neurodegenerative disease models ( St Johnston 2002 ; Matsumoto et al 2003 ; Passarella and Goedert 2018 ; Mishra and Knust 2019 ; Smylla et al 2021 ). We therefore used GMR-Gal4 to drive expression of each construct specifically in eyes, observing for phenotypic neurodegeneration with a scoring system we have used before ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17

Patel,

Alam,

Libohova

et al. 2023

G3: Genes, Genomes, Genetics

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Spinocerebellar Ataxia Type 17 (SCA17) is the most recently identified member of the polyglutamine (polyQ) family of disorders, resulting from abnormal CAG/CAA expansion in the TATA box binding protein (TBP), an initiation factor essential for of all eukaryotic transcription. A largely autosomal dominant inherited disease, SCA17 is unique in both its heterogeneous clinical presentation and low incidence of genetic anticipation, the phenomenon in which subsequent generations inherit longer polyQ expansions that yield earlier and more severe symptom onset. Like other polyQ disease family members, SCA17 patients experience progressive ataxia and dementia, and treatments are limited to preventing symptoms and increasing quality of life. Here, we report two new Drosophila models that express human TBP with polyQ repeats in either wild-type or SCA17 patient range. We find that TBP expression has age- and tissue-specific effects on neurodegeneration, with polyQ-expanded SCA17 protein expression generally having more severe effects. In addition, SCA17 model flies accumulate more aggregation-prone TBP, with a greater proportion localizing to the nucleus. These new lines provide a new resource for the biochemical characterization of SCA17 pathology and the future identification of therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17

Patel,

Alam,

Libohova

et al. 2023

G3: Genes, Genomes, Genetics

View full text Add to dashboard Cite

show abstract

“…The Drosophila eye has been used extensively to assess neural toxicity in a variety of neurodegenerative disease models (ST JOHNSTON 2002;MATSUMOTO et al 2003; PASSARELLA AND GOEDERT 2018; MISHRA AND KNUST 2019;SMYLLA et al 2021). We therefore used GMR-Gal4 to drive expression of each construct specifically in eyes, observing for phenotypic neurodegeneration with a scoring system we have used before (Figure 4A).…”

Section: Constitutive Tbp Expression Reduces Adult Lifespan and Mobil...mentioning

confidence: 99%

Phenotypic defects from the expression of wild-type and pathogenic TATA-Binding Proteins in newDrosophilamodels of Spinocerebellar Ataxia Type 17

Patel,

Alam,

Libohova

et al. 2023

Preprint

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Spinocerebellar Ataxia Type 17 (SCA17) is the most recently identified member of the polyglutamine (polyQ) family of disorders, resulting from abnormal CAG/CAA expansion of TATA box binding protein (TBP), an initiation factor essential for of all eukaryotic transcription. A largely autosomal dominant inherited disease, SCA17 is unique in both its heterogeneous clinical presentation and low incidence of genetic anticipation, the phenomenon in which subsequent generations inherit longer polyQ expansions that yield earlier and more severe symptom onset. Like other polyQ disease family members, SCA17 patients experience progressive ataxia and dementia, and treatments are limited to preventing symptoms and increasing quality of life. Here, we report two newDrosophilamodels that express human TBP with polyQ repeats in either wild-type or SCA17 patient range. We find that TBP expression has age- and tissue-specific effects on neurodegeneration, with polyQ expanded SCA17 protein expression generally having more severe effects. In addition, SCA17 model flies accumulate more aggregation prone TBP, with a greater proportion localizing to the nucleus. These new lines provide a new resource for the biochemical characterization of SCA17 pathology and the future identification of therapeutic targets.

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Progressive degeneration in a newDrosophilamodel of Spinocerebellar Ataxia type 7

Sujkowski,

Ranxhi,

Prifti

et al. 2023

Preprint

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Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder resulting from abnormal expansion of polyglutamine (polyQ) in its disease protein, ataxin-7 (ATXN7). ATXN7 is part of Spt-Ada-Gcn5 acetyltransferase (SAGA), an evolutionarily conserved transcriptional coactivation complex with critical roles in chromatin remodeling, cell signaling, neurodifferentiation, mitochondrial health and autophagy. SCA7 is dominantly inherited and characterized by genetic anticipation and high repeat-length instability. Patients with SCA7 experience progressive ataxia, atrophy, spasticity, and blindness. There is currently no cure for SCA7, and therapies are aimed at alleviating symptoms to increase quality of life. Here, we report novelDrosophilalines of SCA7 with polyQ repeats in wild-type and human disease patient range. We find that ATXN7 expression has age- and polyQ repeat length-dependent reduction in survival and retinal instability, concomitant with increased ATXN7 protein aggregation. These new lines will provide important insight on disease progression that can be used in the future to identify therapeutic targets for SCA7 patients.

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Application of Fluorescent Proteins for Functional Dissection of the Drosophila Visual System

Cited by 4 publications

References 129 publications

Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17

Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17

Phenotypic defects from the expression of wild-type and pathogenic TATA-Binding Proteins in newDrosophilamodels of Spinocerebellar Ataxia Type 17

Progressive degeneration in a newDrosophilamodel of Spinocerebellar Ataxia type 7

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