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Customized Zebrafish Models of Aniridia

Genome sequencing has revealed significant genetic similarities between humans and zebrafish, with 84% of human disease-causing genes having zebrafish counterparts, making zebrafish an ideal animal model for studying inherited eye diseases. Ace Therapeutics successfully constructs PAX6 mutant zebrafish models to simulate human genetic aniridia disease through chemical induction and retroviral insertion. This model helps you understand the molecular mechanisms of aniridia and explore potential effective treatments. We always hope to bring light to the world with you.

Zebrafish Models of Aniridia

What Is Aniridia Ocular Disease?

Aniridia is a widespread inherited developmental eye disorder characterized by changes in eye structure and function that can lead to decreased visual acuity and increased sensitivity to light (photophobia) for which there is currently no treatment. Ocular manifestations include complete or partial iris and foveal hypoplasia, cataracts, early-onset glaucoma, nystagmus, and corneal keratopathy, which can be treated with conservative treatment or surgical intervention. Studies have shown that this congenital eye malformation is associated with a heterozygous mutant gene of human PAX6, which is considered the main transcription factor in early eye development. Over the past few decades, several animal models have been studied to better understand the molecular pathophysiology of aniridia disease, including several mouse and zebrafish strains, as well as human induced pluripotent stem cells (hiPSC). Interestingly, in zebrafish, two PAX6 orthologs are expressed in the eye: pax6a and pax6b. Gene expression ratios vary in different organs and tissues, like PAX6 isoforms in humans. Due to their ease of genetic manipulation, zebrafish are ideal for examining eye development, function, and disease. They help to generate robust eye disease models required for large-scale genetic and drug screening programs.

Fig. 1. Human, mouse, and zebrafish PAX6 gene structure. (Abdolkarimi D, et al., 2022)

Service Overview

Patients with congenital aniridia often display haploinsufficiency of PAX6 and aberrations in genomic regions downstream of PAX6. In recent years, the Ace Therapeutics research team has been working on the research and development of zebrafish models related to human PAX6 mutations. This transgenic zebrafish model facilitates the identification of the PAX6 transcriptional network that drives normal development to help our customers understand the pathophysiology of observed loss-of-function defects.

In addition, our scientists perform amplification via chromatin immunoprecipitation, promoter-reporter assays, and immunohistochemistry to help our clients further understand the mechanisms by which genetic mutations affect the aniridia phenotype and provide promising targets for exploring possible therapeutic interventions.

Explore Ace Therapeutics' Zebrafish Models of Aniridia

Ace Therapeutics offers a range of PAX6 mutant transgenic zebrafish aniridia models. This zebrafish model is mutated in Pax6b and exhibits an aniridia-like phenotype, such as lens and corneal structural abnormalities, corneal thickness, iris hypoplasia, retinal malformations, a shallow anterior chamber, and small eyes.

Ace Therapeutics' transgenic zebrafish aniridia model is achieved by chemical induction (N-ethyl-N-nitrosourea, ENU) and retroviral insertion (CRISPR/Cas9). We provide the following zebrafish aniridia models to customers around the world, including but not limited to:

Tab.1. Ace Therapeutics' zebrafish models of PAX6 mutant genes.

Genotype	Generation of mutation	PAX6 domain	Predominant ocular phenotype
PAX6b^tq253a/PAX6b^tq253a(sri)	ENU-induced	homeodomain	Abnormal cornea; Abnormal lens Iris hypoplasia; Retinal malformations; Shallow anterior chamber; Small eye.
PAX6a^ka709/ PAX6ak^a709	CRISPR/Cas9	homeodomain and proline-serine-threonine domain	Marginal anterior segment dysgenesis; Small eye and lens.
PAX6a^ka709/PAX6a^ka709; PAX6b^tq253a/PAX6b^tq253a	ENU-induced and CRISPR/Cas9	homeodomain and proline-serine-threonine domain	Absent lens; Absent anterior chamber; Corneal endothelium malformation; Small eye.

Ace Therapeutics aims to provide a powerful analytical tool for global customers' aniridia research. If you are interested in our services or need more detailed information, please feel free to contact us. Our experienced scientists are ready to help you!

References

Abdolkarimi D, Cunha DL, Lahne M, et al. PAX6 disease models for aniridia. Indian J Ophthalmol. 2022, 70(12):4119-4129.
Richardson R, Tracey-White D, Webster A, et al. The zebrafish eye-a paradigm for investigating human ocular genetics. Eye (Lond). 2017, 31(1):68-86.

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