Editing African clawed frog (section)

== Use in research ==

''[[Xenopus]]'' embryos and eggs are a popular model system for a wide variety of biological studies, in part because they have the potential to lay eggs throughout the year.<ref name="wallingford"/><ref name="Harland"/><ref>{{Cite web|url=https://www.youtube.com/watch?v=Vtah98djCJU |archive-url=https://ghostarchive.org/varchive/youtube/20211211/Vtah98djCJU| archive-date=11 December 2021 |url-status=live|title=First Frog Genome Sequenced - YouTube|website=www.youtube.com}}{{cbignore}}</ref> This animal is widely used because of its powerful combination of experimental tractability and close evolutionary relationship with humans, at least compared to many model organisms.<ref name="wallingford">{{cite journal |doi=10.1016/j.cub.2010.01.012 |pmid=20334828 |title=Xenopus |journal=Current Biology |volume=20 |issue=6 |pages=R263–4 |year=2010 |last1=Wallingford |first1=John B |last2=Liu |first2=Karen J |last3=Zheng |first3=Yixian |doi-access=free }}</ref><ref name="Harland">{{cite journal |doi=10.1016/j.tig.2011.08.003 |pmid=21963197 |pmc=3601910 |title=Xenopus research: Metamorphosed by genetics and genomics |journal=Trends in Genetics |volume=27 |issue=12 |pages=507–15 |year=2011 |last1=Harland |first1=Richard M |last2=Grainger |first2=Robert M }}</ref>  For a more comprehensive discussion of the use of these frogs in biomedical research, see ''[[Xenopus]]''.

''Xenopus laevis'' is also notable for its use in the first widely used method of [[pregnancy test]]ing. In the 1930s, two South African researchers, [[Hillel Abbe Shapiro|Hillel Shapiro]] and Harry Zwarenstein,<ref>{{Cite journal |last1=Shapiro |first1=Hillel A. |last2=Zwarenstein |first2=Harry |date=March 1935 |title=A test for the early diagnosis of pregnancy |journal=South African Medical Journal |volume=9 |pages=202–4 |url=https://www.cabdirect.org/cabdirect/abstract/19352702067 }}</ref> students of [[Lancelot Hogben]] at the [[University of Cape Town]], discovered that the [[urine]] from pregnant women would induce oocyte production in ''X. laevis'' within 8–12 hours of injection.<ref>{{Cite web|url=https://www.smithsonianmag.com/smart-news/doctors-used-to-use-live-african-frogs-as-pregnancy-tests-64279275/|title=Doctors Used to Use Live African Frogs As Pregnancy Tests|first=Rachel|last=Nuwer|author-link=Rachel Nuwer |website=Smithsonian Magazine}}</ref> This was used as a simple and reliable test up through to the 1960s.<ref>{{Cite web|url=http://old.qi.com/talk/viewtopic.php?t=11158&view=next&sid=cdd207a717368643101ca4f5d27208f0|title=QI Talk Forum {{!}} View topic - Flora and Fauna - Pregnancy tests using frogs|website=old.qi.com|access-date=8 September 2018}}</ref>
In the late 1940s, Carlos Galli Mainini<ref>{{cite journal |last1=Mainini |first1=Carlos Galli |title=Pregnancy test using the male toad |journal=Journal of Clinical Endocrinology & Metabolism |date=1947 |volume=7 |issue=9 |pages=653–8 |doi=10.1210/jcem-7-9-653 |pmid=20264656 |url=https://academic.oup.com/jcem/article-abstract/7/9/653/2720262 }}</ref> found in separate studies that male specimens of ''Xenopus'' and ''Bufo'' could be used to indicate pregnancy<ref>{{cite journal |last1=Sulman |first1=Felix Gad |last2=Sulman |first2=Edith |title=Pregnancy test with the male frog (''Rana ridibunda'') |journal=Journal of Clinical Endocrinology & Metabolism |date=1950 |volume=10 |issue=8 |pages=933–8 |doi=10.1210/jcem-10-8-933 |pmid=15436652 |url=https://academic.oup.com/jcem/article-abstract/10/8/933/2719924 }}</ref> Today, commercially available [[Human chorionic gonadotropin|hCG]] is injected into ''Xenopus'' males and females to induce mating behavior and to breed these frogs in captivity at any time of the year.<ref name="ReferenceA">{{cite book |first=S.L. |last=Green |title=The Laboratory ''Xenopus'' sp |series=The Laboratory Animal Pocket Reference Series |publisher=CRC Press |location= |date=2010 |isbn=978-1-4200-9109-0 |oclc=229022815 |editor-first=M. |editor-last=Suckow}}</ref>

''Xenopus'' has long been an important tool for ''in vivo'' studies in molecular, cell, and developmental biology of vertebrate animals.  However, the wide breadth of ''Xenopus'' research stems from the additional fact that cell-free extracts made from ''Xenopus'' are a premier ''in vitro'' system for studies of fundamental aspects of cell and molecular biology.  Thus, ''Xenopus'' is the only vertebrate model system that allows for high-throughput ''in vivo'' analyses of gene function and high-throughput biochemistry.<ref name="wallingford"/>

''Xenopus'' oocytes are a leading system in their own right for studies of various systems, including ion transport and channel physiology.<ref name="wallingford"/> Xanthos et al 2001 uses oocytes to uncover [[T-box]] expression earlier than previously found in vertebrates.<ref name="Naiche-et-al-2005">{{cite journal | last1=Naiche | first1=L.A. | last2=Harrelson | first2=Zachary | last3=Kelly | first3=Robert G. | last4=Papaioannou | first4=Virginia E. | title=T-Box Genes in Vertebrate Development | journal=[[Annual Review of Genetics]] | publisher=[[Annual Reviews (publisher)|Annual Reviews]] | volume=39 | issue=1 | date=1 December 2005 | issn=0066-4197 | doi=10.1146/annurev.genet.39.073003.105925 | pages=219–239| pmid=16285859 }}</ref>

Although ''X. laevis'' does not have the super short [[generation time]], or genetic simplicity generally desired in genetic [[model organism]]s, it is an important model organism in [[developmental biology]], [[cell biology]], [[toxicology]] and [[neurobiology]]. ''X. laevis'' takes 1 to 2 years to reach [[sexual maturity]] and, like most of its genus, it is [[tetraploid]].   It does have a large and easily manipulated [[embryo]], however. The ease of manipulation in [[amphibia]]n embryos has given them an important place in historical and modern developmental biology.  A related species, ''[[Xenopus tropicalis]]'', is considered a more viable model for genetics, although gene editing protocols have now been perfected for.

[[Roger Wolcott Sperry]] used ''X. laevis'' for his famous experiments describing the development of the visual system. These experiments led to the formulation of the [[chemoaffinity hypothesis]].

''X. laevis'' have been used as a model organism in vertebrae cardiogenesis, human congenital heart defects, and in GWAS studies of congenital heart defects.

''Xenopus'' [[oocyte]]s provide an important expression system for [[molecular biology]]. By injecting [[DNA]] or [[Messenger RNA|mRNA]] into the oocyte or developing embryo, scientists can study the protein products in a controlled system. This allows rapid functional expression of manipulated [[DNA]]s (or [[Messenger RNA|mRNA]]). This is particularly useful in [[electrophysiology]], where the ease of recording from the oocyte makes expression of membrane channels attractive. One challenge of oocyte work is eliminating native proteins that might confound results, such as membrane channels native to the [[oocyte]]. Translation of proteins can be blocked or splicing of pre-mRNA can be modified by injection of [[Morpholino]] antisense oligos into the oocyte (for distribution throughout the embryo) or early embryo (for distribution only into daughter cells of the injected cell).<ref>{{cite journal |doi=10.1002/gene.1042 |pmid=11477685 |title=Comparison of morpholino based translational inhibition during the development of ''Xenopus laevis'' and ''Xenopus tropicalis'' |journal=Genesis |volume=30 |issue=3 |pages=110–3 |year=2001 |last1=Nutt |first1=Stephen L |last2=Bronchain |first2=Odile J |last3=Hartley |first3=Katharine O |last4=Amaya |first4=Enrique |s2cid=22708179 |doi-access= }}</ref>

Extracts from the eggs of ''X. laevis'' frogs are also commonly used for biochemical studies of DNA replication and repair, as these extracts fully support DNA replication and other related processes in a cell-free environment which allows easier manipulation.<ref name="pmid3779837">{{cite journal |vauthors=Blow JJ, Laskey RA |title=Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of ''Xenopus'' eggs |journal=Cell |volume=47 |issue=4 |pages=577–87 |date=November 1986  |pmid=3779837 |doi=10.1016/0092-8674(86)90622-7|s2cid=19018084 }}</ref>

The first vertebrate ever to be cloned was an African clawed frog in 1962,<ref>{{Cite web|url=https://www.nobelprize.org/prizes/medicine/2012/gurdon/facts/|title=The Nobel Prize in Physiology or Medicine 2012|website=NobelPrize.org}}</ref> an experiment for which Sir [[John Gurdon]] was awarded the Nobel Prize in Physiology or Medicine in 2012 "for the discovery that mature cells can be reprogrammed to become pluripotent".<ref>{{Cite web|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/|title=The Nobel Prize in Physiology or Medicine 2012|website=www.nobelprize.org|access-date=20 June 2016}}</ref>

Additionally, four female African clawed frogs and stored sperm were present on the [[Space Shuttle Endeavour|Space Shuttle ''Endeavour'']] when it was launched into space on mission [[STS-47]] on 12 September 1992, so that scientists could test whether reproduction and development could occur normally in zero gravity.<ref>{{cite news|url=https://news.google.com/newspapers?id=5DNQAAAAIBAJ&sjid=2VUDAAAAIBAJ&pg=6865%2C5891665|title=Astronauts Fertilize Frog Eggs: Study tadpole development in space project|newspaper=Ludington Daily News|agency=Associated Press|date=14 September 1992|page=7|access-date=19 January 2024|via=Google News}}</ref><ref>{{cite news|title=Frogs, hornets ready for Endeavour tests|url=https://news.google.com/newspapers?id=84U0AAAAIBAJ&sjid=x6MFAAAAIBAJ&pg=1106%2C4192511|newspaper=Reading Eagle|date=11 September 1992|access-date=19 January 2024|via=Google News|page=A8|agency=Associated Press}}</ref>

''Xenopus laevis'' also serves as an ideal model system for the study of the mechanisms of apoptosis. In fact, [[iodine]] and [[thyroxine]] stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibians [[metamorphosis]], and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog.<ref>{{Cite journal |vauthors=Jewhurst K, Levin M, McLaughlin KA |title=Optogenetic control of apoptosis in targeted tissues of ''Xenopus laevis'' embryos |journal=Journal of Cell Death |volume=7 |pages=25–31 |year=2014 |pmid= 25374461 |doi=10.4137/JCD.S18368 |pmc=4213186}}</ref><ref>{{Cite journal |last=Venturi |first=Sebastiano |title=Evolutionary significance of iodine |journal=Current Chemical Biology |volume=5 |pages=155–162 |year=2011 |issn=1872-3136 |doi=10.2174/187231311796765012 |issue=3}}</ref><ref>{{Cite journal |last=Venturi |first=Sebastiano |title=Iodine, PUFAs and Iodolipids in Health and Disease: An Evolutionary Perspective |journal=Human Evolution |volume= 29 |issue= 1–3 |pages=185–205 |year=2014 |issn=0393-9375}}</ref><ref>{{Cite journal |vauthors=Tamura K, Takayama S, Ishii T, Mawaribuchi S, Takamatsu N, Ito M |title=Apoptosis and differentiation of ''Xenopus'' tail-derived myoblasts by thyroid hormone |journal=Journal of Molecular Endocrinology |volume=54 |number=3 |pages=185–92 |year=2015 |doi= 10.1530/JME-14-0327 |pmid=25791374|doi-access=free }}</ref>

Stem cells of this frog were used to create [[xenobot]]s.

=== Genome sequencing ===
Early work on sequencing of the ''X. laevis'' genome was started when the Wallingford and Marcotte labs obtained funding from the Texas Institute for Drug and Diagnostic Development (TI3D), in conjunction with projects funded by the National Institutes of Health. The work rapidly expanded to include ''de novo'' reconstruction of ''X. laevis'' transcripts, in collaboration with groups around the world donating Illumina [[HiSeq|Hi-Seq RNA sequencing]] datasets. Genome sequencing by the Rokhsar and Harland groups (UC Berkeley) and by Taira and collaborators (University of Tokyo, Japan) gave a major boost to the project, which, with additional contributions from investigators in the Netherlands, Korea, Canada and Australia, led to publication of the genome sequence and its characterization in 2016.<ref>{{cite journal|last1=Session|display-authors=etal |first1=Adam|title=Genome evolution in the allotetraploid frog ''Xenopus laevis'' |journal=Nature |date=19 October 2016|volume=538|issue=7625|pages=336–343|doi=10.1038/nature19840|pmid=27762356|pmc=5313049|bibcode=2016Natur.538..336S }}</ref>

=== As transexpression tool ===
''X. laevis'' oocytes are often used as an easy [[model organism|model]] for the artificially induced [[gene expression|expression]] of [[transgene]]s. For example, they are commonly used when studying [[chloroquine resistance]] produced by specialized [[transport protein|transporter]] mutants.<ref name="Wicht-et-al-2020">{{cite journal |last1=Wicht |first1=Kathryn J. |last2=Mok |first2=Sachel |last3=Fidock |first3=David A. |author-link3=David A. Fidock |date=8 September 2020 |title=Molecular Mechanisms of Drug Resistance in ''Plasmodium falciparum'' Malaria |journal=[[Annual Review of Microbiology]] |publisher=[[Annual Reviews (publisher)|Annual Reviews]] |volume=74 |issue=1 |pages=431–454 |doi=10.1146/annurev-micro-020518-115546 |issn=0066-4227 |pmc=8130186 |pmid=32905757}}</ref> Even so the foreign expression tissue may itself confer some alterations to the expression, and so findings may or may not be entirely identical to native expression: For example, iron has been found by Bakouh et al 2017 to be an important substrate for one such transporter in ''X. l.'' oocytes, but {{as of|2020|lc=yes}} iron is merely ''presumptively'' involved in native expression of the same gene.<ref name="Wicht-et-al-2020" />