Tissue Development Study Builds on Tools from National Xenopus Resource

By Stephanie M. McPherson

The African clawed frog is a great model to learn more about human disease and development. These frogs (Xenopus laevis) produce many transparent embryos, making it easy to observe development and run a number of experiments at a time.

But most impressively, 79 percent of genes associated with human disease have a close cousin in the genes of these frogs. The frog’s genes may not be exactly the same, but they function in similar ways. This means results from disease studies in these frogs have a strong relevance to human disease.

A recent paper in Genetics details how to make the study of these frogs more efficient. This study was possible due to prior experiments conducted at the Marine Biological Laboratory’s National Xenopus Resource (NXR) center.

The research team used the gene-editing technique called CRISPR-Cas to target just one tissue at a time and study how it develops. They precisely targeted and turned off one gene, called lhx1, in one of the frog kidneys. They let the other kidney develop normally, which allowed the frog to act as its own control. They saw that the kidney that lacked functioning lhx1 had interruptions in development.

“These findings establish Xenopus as an efficient, cost-effective model for studying the genetics of developmental processes,” the authors wrote. Since they can now modify tissue-specific genes quickly and efficiently, they can also rapidly test gene function, hastening disease and drug discoveries.

Earlier, a group led by NXR Director and MBL Senior Scientist Marko Horb had developed a tool (a new single-guide RNA) for use in CRISPR gene editing to target a specific gene in Xenopus laevis.

“Xenopus laevis has four copies of each gene, in most cases, rather than two,” says Horb. “The benefit of using CRISPR in X. laevis is the ability to use one single-guide RNA to target all copies of the gene.”

Horb shared his work on this specific single-guide RNA across the Xenopus research community. Rachel Miller of the University of Texas, the corresponding author on the recent Genetics paper, reached out to Horb for more details after learning about the tool from a colleague who had completed MBL’s Embryology course.

“The work described in this paper relates to the work done at the NXR in developing new tools for the wider Xenopus research community,” Horb says. “This is exactly the mission of the NXR.”

Citation: Bridget D. DeLay et al (2018) Tissue-Specific Gene Inactivation in Xenopus laevis: Knockout of lhx1 in the Kidney with CRISPR/Cas9. Genetics DOI: 10.1534/genetics.117.300468