Studies Highlight New Research Approaches at MBL Frog Facility

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By Raleigh McElvery

The clawed frog Xenopus boasts a rich background in biomedical research, yet has only just emerged as a genetic model for human disease — from heart conditions to neurological disorders to cancer. Thanks to recent advances in genome editing, it is possible to create Xenopus mutants and also to manipulate their DNA, mimicking changes in the genetic code that engender human disease.

This month, scientists from the Marine Biological Laboratory (MBL) highlight their research success in three articles in a special issue of Developmental Biology on Xenopus genomics.
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The work was led by Marko E. Horb, associate scientist and director of the National Xenopus Resource (NXR) at the MBL. The NXR provides customized transgenic and mutant frogs to the Xenopus research community, as well as advanced training workshops and research facilities for visiting scientists.

“The NXR interacts with the Xenopus research community to improve the [experimental] tools available, as scientists continue to unpack the molecular basis of human disease,” Horb says.

In the first article, Horb provides a comprehensive review of genome editing in Xenopus and underscores the critical role that the NXR plays in implementing this technology in Xenopus laevis. (The Xenopus laevis genome was published last fall.)

Articles in this special issue focus on one particular X. laevis strain that the NXR provides: the sequenced inbred J strain, which provides a powerful research option when used in tandem with genome editing.

In the second article, Horb’s team put a genome editing technique (TALENS) to the test, using it to snip DNA and create site-specific deletions. This study demonstrated for the first time that injecting TALENs into the Xenopus egg allows for transmission of genetically induced mutations from one generation to the next. Often, genome editing in embryos is mosaic, generating many different mutations in various parts of the body. However, Horb and his team showed that TALENs were more effective when injected into Xenopus oocytes (egg cells) rather than embryos.

“Our goal was uniformity,” Horb explains. “If every cell has the same mutation, we can confidently say that a disease is caused by that mutation. This newfound ability ultimately promotes X. laevis as a viable genetic model.”

The third paper from Horb and colleagues in this issue addresses alternate ways to induce ovulation in Xenopus. The human chorionic gonadotropin (hCG) hormone is commonly used to jumpstart the egg-laying process in research frogs, but product shortages called for recourse. While hCG is only found in human, monkey, and horse, Horb tested a more common hormone called luteinizing hormone (LH). His group found that ovine and human LH offered financially feasible and highly purified options to trigger ovulation in Xenopus females.

“Now the Xenopus community has a published method to turn to in the wake of hGC shortages,” Horb says.

Citations:

Tandon P, Conlon F, Furlow JD, Horb ME (2016) Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling. Developmental Biology, DOI: 10.1016/j.ydbio.2016.04.009

Ratzan W, Falco R, Salanga C, Salanga M, and Horb ME  (2016) Generation of a Xenopus laevis F1 albino J strain by genome editing and oocyte host-transfer. Developmental Biology, DOI: 10.1016/j.ydbio.2016.03.006

Wlizla M, Falco R, Peshkin L, Parlow AF, and Horb ME (2016) Luteinizing Hormone is an effective replacement for hCG to induce ovulation in Xenopus. Developmental Biology, DOI: 10.1016/j.ydbio.2016.05.028

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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.