Reduction of mutant ATXN1 rescues premature death in a conditional SCA1 mouse model

Orengo, James P.; Nitschke, Larissa; Heijden, Meike E van der; Ciaburri, Nicholas A.; Orr, Harry T.; Zoghbi, Huda Y.

doi:10.1172/jci.insight.154442

Cited by 7 publications

(1 citation statement)

References 42 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once phenotypic abnormalities are detected, they could be further investigated at the molecular, cellular, or circuit level in the brain to dissect the basis of the abnormal behavioral manifestations. Moreover, it is recognized that SCAs involve structures beyond the cerebellum and can impair non-cerebellar functions, such as motor neuron degeneration observed in SCA1 patients and SCA1 mouse models [77,78]. Zebrafish can be a useful tool for investigating and identifying therapeutic options for such abnormalities, and these studies can benefit from knowledge obtained from other studies and methodologies investigating these structures in other disorders, such as motor neuron disease modeling in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Models of Rare Neurological Diseases like Spinocerebellar Ataxias (SCAs): Advantages and Limitations

Sarasamma,

Karim,

Orengo

2023

Biology

Self Cite

View full text Add to dashboard Cite

Spinocerebellar ataxia (SCA) is a heterogeneous group of rare familial neurodegenerative disorders that share the key feature of cerebellar ataxia. Clinical heterogeneity, diverse gene mutations and complex neuropathology pose significant challenges for developing effective disease-modifying therapies in SCAs. Without a deep understanding of the molecular mechanisms involved for each SCA, we cannot succeed in developing targeted therapies. Animal models are our best tool to address these issues and several have been generated to study the pathological conditions of SCAs. Among them, zebrafish (Danio rerio) models are emerging as a powerful tool for in vivo study of SCAs, as well as rapid drug screens. In this review, we will summarize recent progress in using zebrafish to study the pathology of SCAs. We will discuss recent advancements on how zebrafish models can further clarify underlying genetic, neuroanatomical, and behavioral pathogenic mechanisms of disease. We highlight their usefulness in rapid drug discovery and large screens. Finally, we will discuss the advantages and limitations of this in vivo model to develop tailored therapeutic strategies for SCA.

show abstract

Section: Discussionmentioning

confidence: 99%