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Developmental Biology Boot Camp

Xenopus Disease Models

Why use Xenopus?

Xenopus has a number of unique advantages as a model organism. The frog embryo develops completely separate the mother, providing a number of unique advantages over other models. One,  experiments can be performed prior to, or just after, fertilization. Two, important stages of embryonic development are easily monitored. Three, experimental manipulations to eggs or embryos are relatively straightforward.

Scientists have utilized these advantages to develop disease models of many human muscle disorders in the frog. Below, each cartoon depiction is individually hyperlinked to the peer-reviewed study it describes. Click to learn more!

 

Digeorge2Holt Oram2CHARGE 2Axonfield Reiger2

Chromosomal locations of common congenital heart diseases in humans. Each chromatid pair is a hyperlink to a Xenopus disease model of the indicated disease.

 

Congenital heart disease (CHD): this disease currently has multiple models in Xenopus, notably those modeled by altering the expression of the genes Tbx1 (dominant negative, resembling DiGeorge syndrome), Tbx5 (by dominant negative and depletion, resembling Holt-Oram syndrome), Pitx2 (by overexpression, resembling Axonfeld-Reiger Syndrome) and Chd7 (by protein depletion, resembling CHARGE syndrome), outlined above. Each of these models manifests cardiac phenotype changes which mirror specific changes occurring in humans with CHD. Additionally, one group in a somewhat recent study aims to develop a model in Xenopus using optical coherence tomography (OCT), a type of high-resolution cross-section microscopy, to measure and quantify heart facial structures of frogs with mutations in CHD candidate genes.

 

Cartoon depiction of major results of a study by Hanel et. al, showing that FRG1 protein-depleted Xenopus tadpoles exhibit reduced segmentation and staining of dermomyotome muscle tissue.
Cartoon depiction of major results of a study by Hanel et. al, showing that FRG1 protein-depleted Xenopus tadpoles exhibit reduced segmentation and staining of dermomyotome muscle tissue.

 

Muscular dystrophy (MD): The leading causative candidate gene for MD in humans is FRG1, which is deleted in facioscapulohumeral forms of MD. Researchers have shown that Xenopus embryos depleted of FRG1 protein develop into tadpoles which exhibit decreased dermomyotome (a muscle tissue precursor during development) staining, reduced muscle segmentation, and loss of hypaxial (ventral) muscle. This is illustrated conceptually in the cartoon above.

 

To learn something about Amyotrophic Lateral Sclerosis (ALS), human muscle tissue from persons with ALS can be transplanted into Xenopus oocyte membranes.
To learn something about Amyotrophic Lateral Sclerosis (ALS), human muscle tissue from persons with ALS can be transplanted into Xenopus oocyte membranes.

 

Amyotrophic lateral sclerosis (ALS): At current, Xenopus has been mostly valuable for modeling ALS by way of transplantation studies, wherein exogenous protein or nucleic acid are injected into Xenopus oocytes. For instance, transplantation of Xenopus oocytes with muscle membranes from ALS patients has been used as an avenue towards drug discovery (method shown above). This highlights another way the Xenopus model organism can be utilized to understand something about human muscle disease.