Did you know that zebrafish are often used in genetic research? Not only do they have the same major organs and tissues as humans do, but zebrafish also share a similar genetic structure and offer an opportunity to understand more about human genetic disorders. According to Medical XPress, researchers from ELTE Eötvös Loránd University in Budapest recently created a zebrafish model of pseudoxanthoma elasticum (PXE), a rare genetic disease causing the calcification of elastic fibers throughout the body. Through using this new model, researchers will not only gain insights into the underlying biology of PXE, but also into potential treatment options, biomarkers, and therapeutic candidates. Check out the full research study in Frontiers in Cell and Developmental Biology.

Zebrafish Research

Normally, ABCC6 gene mutations cause PXE. Thus, zebrafish present a great model, as they have three ABCC6 gene variants: abcc6a, abcc6b.1, and abcc6b.2. These are located on chromosomes 6 and 3 respectively. Once researchers examined these variants, they determined that only the first two are able to provide protein-coding functionality, while the latter is no longer active.

In their research, the researchers used CRISPR to develop and characterize mutant genetic lines in abcc6a and abcc6b.1. As described by LiveScience, CRISPR is:

a simple yet powerful tool for editing genomes [that] allows researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops.

Through this research, researchers found that abcc6a homozygous mutant zebrafish had issues with calcification. In fact, this calcifying factor could be seen in larval stages of zebrafish. As a result, researchers were able to determine that these gene mutations suggest that patients with PXE experience early calcification issues which worsen throughout adulthood. By the end of their study, once the zebrafish matured, researchers noted distorted and mutated skeletal systems due to calcification.

Moving forward, researchers will use the mutant genetic lines developed during this study to evaluate potential therapeutic candidates for patients with PXE.

Pseudoxanthoma Elasticum (PXE)

Although pseudoxanthoma elasticum (PXE) was first identified over 100 years ago, recent research has been making strides in understanding this condition. According to the National Organization for Rare Disorders (NORD):

Pseudoxanthoma elasticum (PXE) is an inherited disorder caused by mutations in the ABCC6 transporter gene that affects connective tissue in some parts of the body. Elastic tissue in the body becomes mineralized; that is, calcium is deposited in the tissue.

PXE can cause calcification in the eyes, skin, and cardiovascular or gastrointestinal systems. Typically, PXE is inherited in an autosomal recessive pattern, meaning patients must receive one defective gene from each parent. Symptoms generally appear in adolescence or early adulthood. Symptoms include:

• Retinal bleeding or scarring
• Arterial narrowing
• Central vision loss
• Cramping and pain during exercise
• Decreased blood flow to the arms and legs
• High blood pressure
• Gastrointestinal bleeding
• Peau d’orange and angioid streaks
  • Note: These are characteristic changes in the retina during the initial stages of PXE. Peau d’orange means that the retina begins to resemble orange skin.
• Pregnancy-related complications
• Yellow papules on the neck, underarms, and flexor areas

Without treatment, PXE can result in blindness and a variety of other health-related issues.