Zebrafish Huntington's Disease Models

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder whose exact pathogenic mechanism is unknown. It can transition from one generation to another. CAG triplet expansion of polyglutamine (PolyQ) tracts on huntingtin protein is primarily involved in HD pathogenesis. In addition to this, several other molecular mechanisms have also been implicated in HD pathology, such as loss of brain-derived neurotrophic factor, mitochondrial dysfunction, and altered synaptic plasticity in medium-sized spiny neurons. But the pathophysiology of HD is not fully understood, which hinders the development of effective treatments. Using zebrafish as a model organism enables scientific advances in understanding HD pathology and hopefully the development of potential treatments in the near future.

The discovery of the zebrafish (Danio rerio) bridges the gap between in vitro and in vivo testing, making neuroscience research easy. The zebrafish possesses many advanced functional genomics, such as human disease, understanding of genetics, neurodegenerative diseases and disorders, and discovery of treatments. It is used to assess mutated genes, the etiology of human disease, and to allow identification of related treatments. Currently, zebrafish are widely used for in vivo screening for various central nervous system (CNS) diseases, such as HD, Alzheimer's disease (AD), Parkinson's disease (PD), and memory deficits. Therefore, this makes the zebrafish an excellent animal model for developing new therapeutic strategies for various CNS diseases.

Fig.1 mHTT-∆N17-exon1 transgenic fish develop a progressive motor behavior phenotype.

Our Zebrafish Huntington's Disease Models

Creative Biogene has established well-established zebrafish HD models that allow real-time monitoring of huntingtin (HTT) aggregate deposition in living vertebrate organisms. Expression of polyQ-amplified htt in zebrafish embryos accumulates in large SDS-insoluble inclusion bodies, reproducing key features of HD pathology. Increased frequency of morphologically abnormal embryos, embryonic lethality and induction of apoptosis can be observed following htt mutation. In addition, our zebrafish HD model can be used to screen small molecule inhibitors of polyQ aggregation and toxicity, explain the possible pathogenesis of HD, and discuss possible potential therapeutic targets, which will help discover new therapeutic approaches to Overcoming zebrafish Huntington's disease progression.

Advantages

• Allows real-time monitoring of HTT aggregate deposition in living vertebrate organisms
• Understanding the role of Htt in neural tube formation
• Predicting key biochemical mechanisms associated with polyQ neurodegenerative disease pathogenesis
• Simple and efficient manipulation of multiple genes at a physiologically relevant level

The utility of our zebrafish models in neurological disease research and in improving screening methods makes treatments and therapies more effective. If you want to know more about the zebrafish HD model, please feel free to contact us.

References

1. Chaturvedi B, et al. A Review on Role of Zebrafish in Huntington's Disease. JPRI. 2022, 34:9-14.
2. Kumar V, Singh C, Singh A. Zebrafish an experimental model of Huntington's disease: molecular aspects, therapeutic targets and current challenges. Mol Biol Rep. 2021, 48(12):8181-8194.
3. Das S, Rajanikant GK. Huntington disease: can a zebrafish trail leave more than a ripple?. Neurosci Biobehav Rev. 2014, 45:258-261.

For research use only. Not intended for any clinical use.